Mutagenetix > Incidental Mutation

Incidental Mutation 'R6327:Vcan'

510486

Institutional Source

Beutler Lab

Gene Symbol

Vcan

Ensembl Gene

ENSMUSG00000021614

Gene Name

versican

Synonyms

PG-M, hdf, DPEAAE, heart defect, Cspg2, 5430420N07Rik

MMRRC Submission

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6327 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

89655312-89742509 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 89704832 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Serine to Threonine at position 670 (S670T)

Ref Sequence

ENSEMBL: ENSMUSP00000105173 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000109543] [ENSMUST00000109544] [ENSMUST00000109546] [ENSMUST00000159910]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000109543

SMART Domains

Protein: ENSMUSP00000105170
Gene: ENSMUSG00000021614

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
IG	29	148	1.4e-7	SMART
LINK	148	245	1.4e-53	SMART
LINK	249	347	8.8e-60	SMART
EGF	351	384	2.72e-7	SMART
EGF_CA	386	422	1.16e-10	SMART
CLECT	428	549	3.08e-34	SMART
CCP	555	611	1.04e-8	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000109544
AA Change: S670T

PolyPhen 2 Score 0.944 (Sensitivity: 0.80; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000105171
Gene: ENSMUSG00000021614
AA Change: S670T

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
IG	29	148	1.4e-7	SMART
LINK	148	245	1.4e-53	SMART
LINK	249	347	8.8e-60	SMART
low complexity region	728	743	N/A	INTRINSIC
low complexity region	1205	1219	N/A	INTRINSIC
EGF	1311	1344	2.72e-7	SMART
EGF_CA	1346	1382	1.16e-10	SMART
CLECT	1388	1509	3.08e-34	SMART
CCP	1515	1571	1.04e-8	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000109546
AA Change: S670T

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000105173
Gene: ENSMUSG00000021614
AA Change: S670T

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
IG	29	148	1.4e-7	SMART
LINK	148	245	1.4e-53	SMART
LINK	249	347	8.8e-60	SMART
low complexity region	728	743	N/A	INTRINSIC
low complexity region	1205	1219	N/A	INTRINSIC
low complexity region	1322	1333	N/A	INTRINSIC
low complexity region	1546	1569	N/A	INTRINSIC
low complexity region	1837	1852	N/A	INTRINSIC
low complexity region	2013	2026	N/A	INTRINSIC
low complexity region	2354	2367	N/A	INTRINSIC
low complexity region	2468	2482	N/A	INTRINSIC
low complexity region	2719	2728	N/A	INTRINSIC
EGF	3050	3083	2.72e-7	SMART
EGF_CA	3085	3121	1.16e-10	SMART
CLECT	3127	3248	3.08e-34	SMART
CCP	3254	3310	1.04e-8	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000159910

SMART Domains

Protein: ENSMUSP00000125446
Gene: ENSMUSG00000021614

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
IG	29	148	1.4e-7	SMART
LINK	148	245	1.4e-53	SMART
LINK	249	347	8.8e-60	SMART
low complexity region	362	373	N/A	INTRINSIC
low complexity region	586	609	N/A	INTRINSIC
low complexity region	877	892	N/A	INTRINSIC
low complexity region	1053	1066	N/A	INTRINSIC
low complexity region	1394	1407	N/A	INTRINSIC
low complexity region	1508	1522	N/A	INTRINSIC
low complexity region	1759	1768	N/A	INTRINSIC
EGF	2090	2123	2.72e-7	SMART
EGF_CA	2125	2161	1.16e-10	SMART
CLECT	2167	2288	3.08e-34	SMART
CCP	2294	2350	1.04e-8	SMART

Meta Mutation Damage Score

0.2182

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.5%
20x: 98.4%

Validation Efficiency

100% (43/43)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the aggrecan/versican proteoglycan family. The protein encoded is a large chondroitin sulfate proteoglycan and is a major component of the extracellular matrix. This protein is involved in cell adhesion, proliferation, proliferation, migration and angiogenesis and plays a central role in tissue morphogenesis and maintenance. Mutations in this gene are the cause of Wagner syndrome type 1. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]
PHENOTYPE: Homozygotes for an insertional mutation exhibit anterior-posterior segmental defects of the heart, lack endocardial cushions of the conus and atrioventricular region, and die and around embryonic day 10.5. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 44 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A2ml1	T	C	6: 128,558,692		probably null	Het
Birc6	C	A	17: 74,662,779	H383Q	probably damaging	Het
C2	C	A	17: 34,864,103	A431S	probably benign	Het
C3ar1	C	T	6: 122,850,146	V371M	probably damaging	Het
Chd1l	G	A	3: 97,587,167	A399V	probably damaging	Het
Ckap2l	A	G	2: 129,285,494	S255P	probably damaging	Het
Clca3a1	T	A	3: 144,730,797	I842F	probably benign	Het
Cmc2	G	T	8: 116,894,157	H28Q	probably damaging	Het
Col11a2	C	T	17: 34,043,317	P176L	probably benign	Het
Csmd3	T	C	15: 47,881,387	D1404G	probably damaging	Het
Dld	G	A	12: 31,332,191	P506S	probably benign	Het
Dsg3	T	C	18: 20,539,870	M866T	probably benign	Het
Ehd1	T	C	19: 6,298,345	I451T	possibly damaging	Het
Fosb	T	C	7: 19,307,227	T114A	probably benign	Het
Foxd4	T	A	19: 24,900,834	M1L	possibly damaging	Het
Fstl5	T	A	3: 76,707,801	I723N	probably benign	Het
Gm10549	C	A	18: 33,464,305		probably benign	Het
Gm11595	G	A	11: 99,772,555	R100C	unknown	Het
Hdlbp	A	G	1: 93,429,464	S299P	possibly damaging	Het
Mast4	G	A	13: 102,761,382	R650C	probably damaging	Het
Micu3	A	G	8: 40,366,197	T306A	probably benign	Het
Mylk2	A	G	2: 152,913,693	Q259R	possibly damaging	Het
Nfkbiz	T	C	16: 55,821,962	N31S	probably damaging	Het
Nisch	A	T	14: 31,171,487		probably benign	Het
Nudt17	T	C	3: 96,707,764		probably benign	Het
Olfr1389	A	C	11: 49,431,001	H175P	probably damaging	Het
Olfr292	T	C	7: 86,694,552	V32A	probably benign	Het
Olfr541	T	C	7: 140,704,703	W151R	probably damaging	Het
Oprm1	A	C	10: 6,830,063	I242L	probably damaging	Het
Otud6b	A	G	4: 14,826,496		probably benign	Het
Pamr1	A	T	2: 102,642,174	D606V	probably damaging	Het
Pcf11	T	C	7: 92,659,609		probably benign	Het
Pom121l2	T	C	13: 21,982,332	S258P	probably damaging	Het
Rcsd1	T	A	1: 165,655,834	D196V	possibly damaging	Het
Sbf2	C	T	7: 110,441,552	R356Q	probably damaging	Het
Serpinf1	A	G	11: 75,413,905		probably null	Het
Slc22a30	T	G	19: 8,335,722		probably benign	Het
Strn4	G	T	7: 16,816,459	S36I	probably benign	Het
Taar6	A	G	10: 23,985,279	L123P	probably damaging	Het
Thbs1	G	T	2: 118,112,656	R5L	unknown	Het
Timp3	T	C	10: 86,345,786	Y174H	probably benign	Het
Trpm2	C	T	10: 77,932,227	V813M	probably damaging	Het
Uox	C	T	3: 146,624,577	R163*	probably null	Het
Vmn1r65	A	T	7: 6,008,652	N194K	possibly damaging	Het

Other mutations in Vcan

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00434:Vcan	APN	13	89704702	missense	probably damaging	1.00
IGL00502:Vcan	APN	13	89692319	missense	probably benign
IGL00504:Vcan	APN	13	89691275	missense	possibly damaging	0.70
IGL00566:Vcan	APN	13	89688979	missense	probably benign	0.01
IGL00701:Vcan	APN	13	89703726	missense	probably benign
IGL00743:Vcan	APN	13	89725306	missense	probably damaging	0.98
IGL00962:Vcan	APN	13	89662052	missense	probably damaging	1.00
IGL01085:Vcan	APN	13	89679958	missense	probably damaging	1.00
IGL01317:Vcan	APN	13	89691668	missense	probably benign	0.00
IGL01349:Vcan	APN	13	89703943	missense	probably damaging	0.98
IGL01391:Vcan	APN	13	89704169	missense	probably benign	0.19
IGL01644:Vcan	APN	13	89688675	missense	probably benign	0.13
IGL01657:Vcan	APN	13	89690586	missense	probably damaging	1.00
IGL01707:Vcan	APN	13	89689745	missense	probably damaging	1.00
IGL01764:Vcan	APN	13	89725388	missense	probably damaging	1.00
IGL01920:Vcan	APN	13	89689205	missense	probably benign	0.04
IGL01989:Vcan	APN	13	89689359	missense	possibly damaging	0.86
IGL01999:Vcan	APN	13	89684438	missense	probably damaging	1.00
IGL02083:Vcan	APN	13	89725565	missense	probably damaging	1.00
IGL02160:Vcan	APN	13	89684493	missense	probably damaging	1.00
IGL02217:Vcan	APN	13	89703077	missense	probably damaging	1.00
IGL02522:Vcan	APN	13	89704849	missense	probably benign	0.00
IGL02527:Vcan	APN	13	89690657	missense	possibly damaging	0.95
IGL02926:Vcan	APN	13	89688623	missense	probably damaging	0.98
IGL03061:Vcan	APN	13	89703275	missense	probably benign	0.25
IGL03331:Vcan	APN	13	89661932	missense	probably damaging	1.00
IGL03352:Vcan	APN	13	89705006	missense	probably benign	0.00
R0041:Vcan	UTSW	13	89661985	missense	probably damaging	1.00
R0102:Vcan	UTSW	13	89703668	missense	probably benign	0.01
R0102:Vcan	UTSW	13	89703668	missense	probably benign	0.01
R0109:Vcan	UTSW	13	89678073	critical splice donor site	probably null
R0139:Vcan	UTSW	13	89691261	missense	probably damaging	1.00
R0295:Vcan	UTSW	13	89712191	missense	probably benign	0.06
R0375:Vcan	UTSW	13	89691275	missense	probably damaging	0.99
R0379:Vcan	UTSW	13	89703546	missense	probably damaging	0.99
R0457:Vcan	UTSW	13	89703199	missense	possibly damaging	0.78
R0482:Vcan	UTSW	13	89678145	missense	probably damaging	1.00
R0485:Vcan	UTSW	13	89704660	missense	possibly damaging	0.92
R0532:Vcan	UTSW	13	89703772	missense	probably damaging	0.99
R0561:Vcan	UTSW	13	89712253	missense	probably damaging	1.00
R0561:Vcan	UTSW	13	89731464	missense	possibly damaging	0.86
R0636:Vcan	UTSW	13	89704706	missense	probably damaging	0.99
R0636:Vcan	UTSW	13	89712267	missense	probably damaging	1.00
R0680:Vcan	UTSW	13	89679822	missense	probably damaging	1.00
R0849:Vcan	UTSW	13	89704953	missense	possibly damaging	0.75
R1006:Vcan	UTSW	13	89685077	critical splice donor site	probably null
R1104:Vcan	UTSW	13	89692410	missense	probably damaging	1.00
R1118:Vcan	UTSW	13	89705663	missense	probably damaging	1.00
R1137:Vcan	UTSW	13	89704303	missense	probably damaging	1.00
R1199:Vcan	UTSW	13	89679794	splice site	probably null
R1219:Vcan	UTSW	13	89679904	missense	probably damaging	1.00
R1296:Vcan	UTSW	13	89657556	missense	probably damaging	1.00
R1332:Vcan	UTSW	13	89693055	missense	probably damaging	1.00
R1336:Vcan	UTSW	13	89693055	missense	probably damaging	1.00
R1403:Vcan	UTSW	13	89688484	missense	probably benign	0.00
R1403:Vcan	UTSW	13	89688484	missense	probably benign	0.00
R1546:Vcan	UTSW	13	89692956	missense	probably damaging	0.99
R1604:Vcan	UTSW	13	89689661	missense	probably benign	0.42
R1616:Vcan	UTSW	13	89705663	missense	probably damaging	1.00
R1636:Vcan	UTSW	13	89703667	missense	possibly damaging	0.90
R1654:Vcan	UTSW	13	89661946	missense	probably damaging	1.00
R1680:Vcan	UTSW	13	89703547	missense	probably benign	0.19
R1694:Vcan	UTSW	13	89688483	missense	probably damaging	0.98
R1712:Vcan	UTSW	13	89721775	missense	probably damaging	1.00
R1754:Vcan	UTSW	13	89704735	missense	probably benign	0.01
R1756:Vcan	UTSW	13	89691681	missense	probably benign	0.05
R1824:Vcan	UTSW	13	89705212	missense	possibly damaging	0.75
R1852:Vcan	UTSW	13	89705392	missense	probably damaging	0.99
R1868:Vcan	UTSW	13	89690871	missense	probably benign	0.12
R1920:Vcan	UTSW	13	89693015	missense	probably damaging	1.00
R1932:Vcan	UTSW	13	89705534	missense	possibly damaging	0.78
R1934:Vcan	UTSW	13	89702926	missense	probably damaging	1.00
R1942:Vcan	UTSW	13	89703424	missense	probably benign	0.01
R1964:Vcan	UTSW	13	89692742	missense	probably benign	0.02
R1970:Vcan	UTSW	13	89689038	missense	probably damaging	1.00
R2045:Vcan	UTSW	13	89690985	missense	probably benign	0.00
R2110:Vcan	UTSW	13	89693303	missense	probably damaging	1.00
R2111:Vcan	UTSW	13	89693303	missense	probably damaging	1.00
R2112:Vcan	UTSW	13	89693303	missense	probably damaging	1.00
R2136:Vcan	UTSW	13	89689737	missense	probably damaging	1.00
R2158:Vcan	UTSW	13	89703529	missense	possibly damaging	0.68
R2376:Vcan	UTSW	13	89703410	missense	possibly damaging	0.80
R2385:Vcan	UTSW	13	89689449	missense	probably damaging	1.00
R2443:Vcan	UTSW	13	89704675	missense	probably damaging	1.00
R2876:Vcan	UTSW	13	89704237	missense	probably damaging	1.00
R3607:Vcan	UTSW	13	89703301	missense	probably damaging	0.98
R4042:Vcan	UTSW	13	89692543	missense	probably benign	0.35
R4043:Vcan	UTSW	13	89692543	missense	probably benign	0.35
R4044:Vcan	UTSW	13	89692543	missense	probably benign	0.35
R4065:Vcan	UTSW	13	89679887	missense	probably damaging	1.00
R4161:Vcan	UTSW	13	89685158	missense	probably damaging	1.00
R4178:Vcan	UTSW	13	89725547	missense	probably damaging	1.00
R4290:Vcan	UTSW	13	89725486	missense	probably damaging	1.00
R4530:Vcan	UTSW	13	89704028	missense	probably damaging	0.97
R4666:Vcan	UTSW	13	89679934	missense	probably damaging	1.00
R4785:Vcan	UTSW	13	89705789	missense	probably damaging	1.00
R4870:Vcan	UTSW	13	89704739	missense	probably benign	0.01
R4973:Vcan	UTSW	13	89688842	missense	probably benign	0.30
R5037:Vcan	UTSW	13	89703977	missense	probably damaging	1.00
R5104:Vcan	UTSW	13	89657472	intron	probably benign
R5124:Vcan	UTSW	13	89725517	missense	probably damaging	1.00
R5129:Vcan	UTSW	13	89690240	missense	probably damaging	1.00
R5198:Vcan	UTSW	13	89690872	missense	probably damaging	1.00
R5240:Vcan	UTSW	13	89692532	missense	probably benign	0.08
R5254:Vcan	UTSW	13	89691600	missense	probably damaging	0.99
R5280:Vcan	UTSW	13	89690286	missense	probably benign	0.00
R5522:Vcan	UTSW	13	89691810	missense	possibly damaging	0.62
R5557:Vcan	UTSW	13	89703112	missense	possibly damaging	0.77
R5568:Vcan	UTSW	13	89688671	missense	probably damaging	1.00
R5578:Vcan	UTSW	13	89691503	missense	probably benign	0.01
R5627:Vcan	UTSW	13	89691135	frame shift	probably null
R5687:Vcan	UTSW	13	89678134	missense	probably damaging	1.00
R5752:Vcan	UTSW	13	89679950	missense	probably damaging	1.00
R5879:Vcan	UTSW	13	89703952	missense	probably damaging	0.99
R5941:Vcan	UTSW	13	89692691	missense	probably damaging	0.98
R6113:Vcan	UTSW	13	89657536	nonsense	probably null
R6135:Vcan	UTSW	13	89689926	missense	probably benign	0.36
R6252:Vcan	UTSW	13	89691220	nonsense	probably null
R6280:Vcan	UTSW	13	89725373	missense	probably damaging	1.00
R6317:Vcan	UTSW	13	89691597	missense	probably benign	0.22
R6460:Vcan	UTSW	13	89690687	missense	possibly damaging	0.61
R6669:Vcan	UTSW	13	89704731	missense	probably benign	0.21
R6744:Vcan	UTSW	13	89705182	missense	probably damaging	1.00
R6819:Vcan	UTSW	13	89705125	missense	probably benign	0.00
R6880:Vcan	UTSW	13	89712381	missense	probably damaging	1.00
R6956:Vcan	UTSW	13	89689431	missense	probably damaging	0.99
R6971:Vcan	UTSW	13	89678133	missense	probably damaging	1.00
R6985:Vcan	UTSW	13	89679956	missense	probably damaging	1.00
R6994:Vcan	UTSW	13	89693407	missense	possibly damaging	0.94
R6997:Vcan	UTSW	13	89690618	missense	probably damaging	0.98
R7029:Vcan	UTSW	13	89690241	missense	probably damaging	1.00
R7066:Vcan	UTSW	13	89705686	missense	probably damaging	1.00
R7156:Vcan	UTSW	13	89689110	missense	possibly damaging	0.95
R7171:Vcan	UTSW	13	89725591	missense	probably damaging	1.00
R7176:Vcan	UTSW	13	89688936	missense	probably benign	0.01
R7229:Vcan	UTSW	13	89705270	missense	possibly damaging	0.87
R7250:Vcan	UTSW	13	89721686	missense	probably damaging	1.00
R7250:Vcan	UTSW	13	89731457	critical splice donor site	probably null
R7262:Vcan	UTSW	13	89705161	missense	possibly damaging	0.62
R7289:Vcan	UTSW	13	89692733	nonsense	probably null
R7299:Vcan	UTSW	13	89705266	missense	probably benign
R7301:Vcan	UTSW	13	89705266	missense	probably benign
R7425:Vcan	UTSW	13	89689832	missense	probably damaging	0.99
R7514:Vcan	UTSW	13	89704118	missense	probably damaging	0.97
R7579:Vcan	UTSW	13	89692458	missense	probably damaging	1.00
R7618:Vcan	UTSW	13	89692223	missense	probably damaging	0.99
R7655:Vcan	UTSW	13	89685114	missense	probably damaging	1.00
R7656:Vcan	UTSW	13	89685114	missense	probably damaging	1.00
R7676:Vcan	UTSW	13	89691789	missense	probably damaging	1.00
R7719:Vcan	UTSW	13	89704619	missense	probably damaging	0.98
R7753:Vcan	UTSW	13	89689323	missense	probably damaging	1.00
R7762:Vcan	UTSW	13	89692937	missense	probably damaging	1.00
R7778:Vcan	UTSW	13	89688654	missense	probably damaging	1.00
R7824:Vcan	UTSW	13	89688654	missense	probably damaging	1.00
R7995:Vcan	UTSW	13	89691858	missense	probably benign
R7998:Vcan	UTSW	13	89704327	missense	probably damaging	1.00
R8033:Vcan	UTSW	13	89704360	missense	probably benign	0.04
R8061:Vcan	UTSW	13	89657290	missense	probably benign	0.45
R8103:Vcan	UTSW	13	89657658	missense	probably damaging	1.00
R8103:Vcan	UTSW	13	89703320	nonsense	probably null
R8124:Vcan	UTSW	13	89704254	missense	possibly damaging	0.93
R8162:Vcan	UTSW	13	89704987	nonsense	probably null
R8166:Vcan	UTSW	13	89692736	missense	probably benign	0.02
R8274:Vcan	UTSW	13	89704970	missense	probably benign	0.02
R8284:Vcan	UTSW	13	89704335	missense	possibly damaging	0.68
R8417:Vcan	UTSW	13	89688743	missense	probably benign	0.19
R8696:Vcan	UTSW	13	89691098	missense	probably benign	0.00
R8738:Vcan	UTSW	13	89692320	missense	probably benign	0.17
R8792:Vcan	UTSW	13	89692111	missense	possibly damaging	0.91
R8887:Vcan	UTSW	13	89704907	missense	probably benign
R9049:Vcan	UTSW	13	89678105	missense	probably damaging	1.00
R9074:Vcan	UTSW	13	89691027	missense	possibly damaging	0.95
R9095:Vcan	UTSW	13	89704525	missense	probably benign	0.32
R9172:Vcan	UTSW	13	89679931	missense	probably damaging	1.00
R9199:Vcan	UTSW	13	89690496	nonsense	probably null
R9259:Vcan	UTSW	13	89690870	missense	probably damaging	0.99
R9455:Vcan	UTSW	13	89689333	missense	probably damaging	1.00
R9476:Vcan	UTSW	13	89703412	missense	possibly damaging	0.95
R9477:Vcan	UTSW	13	89693009	missense	probably damaging	1.00
R9555:Vcan	UTSW	13	89691540	missense
R9579:Vcan	UTSW	13	89689594	missense	possibly damaging	0.67
R9606:Vcan	UTSW	13	89705372	missense	probably damaging	1.00
R9645:Vcan	UTSW	13	89692962	missense	probably benign	0.00
R9659:Vcan	UTSW	13	89691741	missense	probably damaging	0.99
R9766:Vcan	UTSW	13	89691128	missense	probably benign	0.00
R9778:Vcan	UTSW	13	89689811	missense	probably damaging	1.00
X0058:Vcan	UTSW	13	89692493	missense	probably benign	0.21
X0065:Vcan	UTSW	13	89705749	missense	probably damaging	0.96
Z1176:Vcan	UTSW	13	89692571	missense	probably benign	0.10
Z1177:Vcan	UTSW	13	89703524	missense	probably benign	0.00
Z1177:Vcan	UTSW	13	89703788	nonsense	probably null
Z1177:Vcan	UTSW	13	89704073	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CAGGGGAAACAGATTCTGTCC -3'
(R):5'- ATGCTTGGCACAGATAGATCACTG -3'

Sequencing Primer
(F):5'- AGGGGAAACAGATTCTGTCCTTTCC -3'
(R):5'- CACTGATAGATAAAGAGAAAGAACCC -3'

Posted On

2018-04-02