Mutagenetix > Incidental Mutation

Incidental Mutation 'R1768:Dna2'

194607

Institutional Source

Beutler Lab

Gene Symbol

Dna2

Ensembl Gene

ENSMUSG00000036875

Gene Name

DNA replication helicase/nuclease 2

Synonyms

E130315B21Rik, Dna2l

MMRRC Submission

039799-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1768 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

62947026-62974185 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 62957084 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 293 (Y293H)

Ref Sequence

ENSEMBL: ENSMUSP00000115750 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000092462] [ENSMUST00000131422]

AlphaFold

Q6ZQJ5

Predicted Effect

probably benign
Transcript: ENSMUST00000092462
AA Change: Y293H

PolyPhen 2 Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)

SMART Domains

Protein: ENSMUSP00000090119
Gene: ENSMUSG00000036875
AA Change: Y293H

Domain	Start	End	E-Value	Type
low complexity region	4	15	N/A	INTRINSIC
Pfam:Dna2	68	284	4.7e-75	PFAM
Pfam:PDDEXK_1	125	404	4.3e-13	PFAM
Pfam:AAA_11	626	799	6.7e-42	PFAM
Pfam:AAA_30	626	848	1.1e-15	PFAM
Pfam:AAA_19	633	709	5.7e-9	PFAM
Pfam:AAA_12	806	944	4.1e-20	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000129785

Predicted Effect

probably benign
Transcript: ENSMUST00000131422
AA Change: Y293H

PolyPhen 2 Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)

SMART Domains

Protein: ENSMUSP00000115750
Gene: ENSMUSG00000036875
AA Change: Y293H

Domain	Start	End	E-Value	Type
low complexity region	4	15	N/A	INTRINSIC
Pfam:Dna2	72	283	8.2e-65	PFAM
Pfam:PDDEXK_1	125	404	3e-11	PFAM
Pfam:AAA_11	626	732	7.8e-17	PFAM
Pfam:AAA_30	626	848	1.3e-15	PFAM
Pfam:AAA_19	633	709	6.2e-9	PFAM
Pfam:AAA_11	722	799	1.2e-21	PFAM
Pfam:AAA_12	806	1020	5.3e-57	PFAM

Meta Mutation Damage Score

0.1718

Coding Region Coverage

1x: 97.4%
3x: 96.9%
10x: 95.3%
20x: 92.4%

Validation Efficiency

91% (107/117)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the DNA2/NAM7 helicase family. The encoded protein is a conserved helicase/nuclease involved in the maintenance of mitochondrial and nuclear DNA stability. Mutations in this gene are associated with autosomal dominant progressive external ophthalmoplegia-6 (PEOA6) and Seckel syndrome 8. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit embryonic lethality before E7.5. Mice heterozygous for the allele exhibit shortened telomeres, chromosome segregation errors and increased tumor incidence associated with aneuploidy. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 112 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4921524L21Rik	G	C	18: 6,623,470	R60P	possibly damaging	Het
Aox2	T	A	1: 58,354,195	C1199S	probably benign	Het
Arhgap18	G	A	10: 26,887,861	M482I	probably damaging	Het
Arhgap18	G	T	10: 26,887,862	A483S	probably damaging	Het
Arid4a	G	A	12: 71,075,338	S509N	probably benign	Het
BC051019	T	C	7: 109,723,174	T38A	probably benign	Het
Bcam	T	C	7: 19,765,618	N192S	probably null	Het
Bend5	A	T	4: 111,454,241	K351*	probably null	Het
Bicdl2	T	A	17: 23,665,949	M208K	probably damaging	Het
Ccdc155	T	A	7: 45,188,803		probably null	Het
Ccp110	A	T	7: 118,726,024		probably null	Het
Cdc6	A	T	11: 98,912,217	T328S	probably damaging	Het
Cdk5rap2	G	T	4: 70,307,233	N558K	probably benign	Het
Cdkn1c	C	T	7: 143,459,121	R146K	probably benign	Het
Ceacam18	G	A	7: 43,648,494	C371Y	probably benign	Het
Cep95	T	A	11: 106,806,351	C233*	probably null	Het
Chrnd	A	G	1: 87,194,928	I144V	probably benign	Het
Col6a4	T	A	9: 106,080,100	Q175L	probably benign	Het
Cym	A	T	3: 107,213,500	V263E	probably damaging	Het
Cyp2a4	G	T	7: 26,312,772	V327F	possibly damaging	Het
Dhx29	T	A	13: 112,948,240	M664K	probably damaging	Het
Dlec1	T	G	9: 119,146,007		probably null	Het
Dnase1l3	T	A	14: 7,974,104	N196Y	probably damaging	Het
Eea1	T	A	10: 95,996,960	D222E	probably damaging	Het
Efcab14	A	T	4: 115,752,919		probably null	Het
Entpd5	C	T	12: 84,386,211	R189H	probably benign	Het
Exoc4	A	T	6: 33,758,050	K534M	probably damaging	Het
Extl1	T	A	4: 134,371,138	Y194F	probably benign	Het
Eya1	A	G	1: 14,253,075	L161S	possibly damaging	Het
Fam163b	T	C	2: 27,112,862	E41G	possibly damaging	Het
Fam180a	A	C	6: 35,315,352	S40A	probably benign	Het
Fbxl4	T	C	4: 22,385,950	S186P	probably benign	Het
Fbxw19	A	T	9: 109,494,772	L45*	probably null	Het
Fgf14	G	T	14: 124,676,512	T69N	probably benign	Het
Flt1	A	G	5: 147,672,709	Y432H	probably damaging	Het
Frmd4b	A	T	6: 97,306,764	L374Q	possibly damaging	Het
G6pc2	T	A	2: 69,222,977	V125D	probably damaging	Het
Gna15	A	T	10: 81,512,120	L164Q	probably damaging	Het
Gnaz	C	A	10: 74,991,870	D151E	possibly damaging	Het
Has1	T	C	17: 17,850,300	T120A	probably benign	Het
Hectd4	T	A	5: 121,358,303	D3919E	possibly damaging	Het
Hs3st5	A	G	10: 36,833,169	I233M	probably benign	Het
Ilf3	T	C	9: 21,403,142		probably benign	Het
Inpp5b	T	A	4: 124,793,276	L765*	probably null	Het
Insr	A	T	8: 3,159,561	I1174N	probably damaging	Het
Kcnq3	A	G	15: 66,005,906	L445P	probably damaging	Het
Kctd20	A	T	17: 28,962,850	N159Y	probably damaging	Het
Kctd20	A	T	17: 28,966,781	D366V	probably damaging	Het
Klk15	T	C	7: 43,938,333		probably benign	Het
Lama4	T	G	10: 39,103,501	N1658K	possibly damaging	Het
Lonrf2	G	A	1: 38,813,276	P165S	probably benign	Het
Mas1	T	C	17: 12,841,699	Y279C	probably damaging	Het
Mast2	G	T	4: 116,306,959	D1747E	probably damaging	Het
Mest	G	A	6: 30,745,139	M235I	probably benign	Het
Mfsd6	A	G	1: 52,660,805		probably null	Het
Mllt10	T	A	2: 18,162,846	S449R	probably damaging	Het
Mon2	T	A	10: 123,013,763	T1211S	probably benign	Het
Mrnip	G	A	11: 50,176,861	C27Y	probably damaging	Het
Myh15	A	T	16: 49,163,135	T1538S	probably benign	Het
Nfatc2ip	A	G	7: 126,390,462	V250A	probably benign	Het
Npy1r	A	G	8: 66,704,525	D199G	possibly damaging	Het
Numbl	A	G	7: 27,280,954	T454A	probably benign	Het
Nutm2	T	G	13: 50,473,116	F436V	probably damaging	Het
Olfr1112	T	A	2: 87,191,698	S4T	probably benign	Het
Olfr330	A	G	11: 58,529,776	L70P	probably damaging	Het
Olfr458	A	G	6: 42,460,677	L114S	probably damaging	Het
Olfr556	A	G	7: 102,670,301	Y127C	probably damaging	Het
Olfr631	C	T	7: 103,929,725	R301*	probably null	Het
Olfr64	A	G	7: 103,893,277	S153P	probably benign	Het
Olfr676	A	G	7: 105,035,950	S251G	probably benign	Het
Olfr707	A	T	7: 106,891,977		probably null	Het
Olfr707	G	T	7: 106,891,978	L44M	probably damaging	Het
Olfr876	T	A	9: 37,804,303	Y131N	probably damaging	Het
Opa1	T	C	16: 29,620,810	S773P	probably benign	Het
Pde8a	G	C	7: 81,300,723		probably null	Het
Pgam1	T	C	19: 41,917,705	F232S	probably damaging	Het
Pgk1	T	A	X: 106,200,308	V303E	possibly damaging	Het
Pirb	A	T	7: 3,717,190	C395S	probably damaging	Het
Plxnc1	C	T	10: 94,844,322	V824I	probably benign	Het
Ppp6r1	A	G	7: 4,633,692		probably null	Het
Rapgef4	C	A	2: 72,225,787		probably benign	Het
Rars	T	A	11: 35,809,638	T539S	probably damaging	Het
Rbm44	G	T	1: 91,153,957		probably null	Het
RP23-114B10.6	T	C	8: 69,373,558	I119M	unknown	Het
Samd4b	A	G	7: 28,413,892	I216T	probably benign	Het
Serpine2	A	C	1: 79,816,815	F134V	probably damaging	Het
Shmt1	A	G	11: 60,792,964	Y341H	probably damaging	Het
Slc23a2	C	A	2: 132,075,641	V226F	probably benign	Het
Slc23a4	A	G	6: 34,956,961	I69T	probably damaging	Het
Slc37a1	C	A	17: 31,333,678	T319K	possibly damaging	Het
Slc6a4	A	T	11: 77,013,252	T178S	probably damaging	Het
Smarca4	G	A	9: 21,701,183	A1588T	possibly damaging	Het
Spag17	A	T	3: 100,027,352	Y650F	possibly damaging	Het
Stab2	C	T	10: 87,003,008	G65S	probably damaging	Het
Stambpl1	C	G	19: 34,226,721	N70K	probably damaging	Het
Stip1	C	A	19: 7,021,797	C471F	probably damaging	Het
Taf1	T	C	X: 101,540,894	S223P	probably benign	Het
Tchh	C	A	3: 93,443,575	N107K	possibly damaging	Het
Tenm3	A	C	8: 48,232,104	H2432Q	probably damaging	Het
Tmem243	A	G	5: 9,118,548	N110S	probably damaging	Het
Toe1	A	T	4: 116,804,879	I306F	probably benign	Het
Trank1	G	A	9: 111,392,927	V2911M	probably damaging	Het
Trpm4	A	G	7: 45,308,612	I811T	probably damaging	Het
Tspear	T	A	10: 77,875,116		probably null	Het
Ttc28	A	T	5: 111,277,168	I1589F	possibly damaging	Het
Tubgcp3	A	G	8: 12,649,686		probably benign	Het
U2af2	C	A	7: 5,067,545	R78S	probably benign	Het
Wdr17	A	T	8: 54,673,654	D388E	possibly damaging	Het
Wdr3	A	T	3: 100,153,870	S261T	probably benign	Het
Zfp667	A	G	7: 6,305,067	N245D	possibly damaging	Het
Zfp692	A	G	11: 58,310,176		probably benign	Het
Zfp729a	T	C	13: 67,619,251	H953R	probably benign	Het

Other mutations in Dna2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00329:Dna2	APN	10	62966443	missense	probably damaging	1.00
IGL00972:Dna2	APN	10	62950823	missense	probably benign	0.13
IGL01511:Dna2	APN	10	62955314	missense	possibly damaging	0.69
IGL01600:Dna2	APN	10	62950806	missense	probably damaging	0.96
IGL02016:Dna2	APN	10	62960412	missense	probably benign	0.00
IGL02049:Dna2	APN	10	62957036	missense	probably damaging	0.99
IGL02069:Dna2	APN	10	62958994	missense	probably benign	0.00
IGL02438:Dna2	APN	10	62957062	missense	possibly damaging	0.92
IGL02743:Dna2	APN	10	62957042	missense	possibly damaging	0.90
IGL02800:Dna2	APN	10	62961725	critical splice donor site	probably null
IGL02936:Dna2	APN	10	62957100	missense	probably damaging	1.00
supercoiled	UTSW	10	62971993	splice site	probably null
R0308:Dna2	UTSW	10	62956974	missense	probably damaging	0.98
R0528:Dna2	UTSW	10	62958131	missense	probably benign	0.00
R0669:Dna2	UTSW	10	62956989	missense	probably damaging	1.00
R0697:Dna2	UTSW	10	62949341	missense	probably benign	0.01
R0831:Dna2	UTSW	10	62959329	nonsense	probably null
R0839:Dna2	UTSW	10	62969782	missense	probably damaging	1.00
R0991:Dna2	UTSW	10	62949187	missense	probably benign	0.08
R0992:Dna2	UTSW	10	62949187	missense	probably benign	0.08
R1054:Dna2	UTSW	10	62963823	missense	possibly damaging	0.84
R1082:Dna2	UTSW	10	62949187	missense	probably benign	0.08
R1084:Dna2	UTSW	10	62949187	missense	probably benign	0.08
R1184:Dna2	UTSW	10	62959198	missense	probably benign	0.00
R1193:Dna2	UTSW	10	62949187	missense	probably benign	0.08
R1196:Dna2	UTSW	10	62949187	missense	probably benign	0.08
R1226:Dna2	UTSW	10	62960424	missense	possibly damaging	0.88
R1561:Dna2	UTSW	10	62949187	missense	probably benign	0.08
R1562:Dna2	UTSW	10	62949187	missense	probably benign	0.08
R1566:Dna2	UTSW	10	62949187	missense	probably benign	0.08
R1568:Dna2	UTSW	10	62949187	missense	probably benign	0.08
R1598:Dna2	UTSW	10	62961657	missense	probably damaging	0.99
R2075:Dna2	UTSW	10	62969822	missense	probably benign	0.20
R3125:Dna2	UTSW	10	62949202	missense	possibly damaging	0.66
R3763:Dna2	UTSW	10	62966797	missense	probably damaging	1.00
R4059:Dna2	UTSW	10	62956989	missense	probably damaging	1.00
R5002:Dna2	UTSW	10	62950842	missense	probably damaging	1.00
R5160:Dna2	UTSW	10	62947154	missense	probably benign
R5567:Dna2	UTSW	10	62966673	missense	possibly damaging	0.89
R5775:Dna2	UTSW	10	62949242	missense	possibly damaging	0.94
R5984:Dna2	UTSW	10	62962506	critical splice donor site	probably null
R6604:Dna2	UTSW	10	62967743	critical splice donor site	probably null
R6702:Dna2	UTSW	10	62973294	missense	possibly damaging	0.89
R6703:Dna2	UTSW	10	62973294	missense	possibly damaging	0.89
R6812:Dna2	UTSW	10	62959341	missense	probably benign	0.18
R6820:Dna2	UTSW	10	62964904	missense	possibly damaging	0.93
R6919:Dna2	UTSW	10	62957003	missense	probably damaging	1.00
R7029:Dna2	UTSW	10	62963994	missense	probably damaging	1.00
R7082:Dna2	UTSW	10	62954317	missense	possibly damaging	0.71
R7508:Dna2	UTSW	10	62971993	splice site	probably null
R7513:Dna2	UTSW	10	62971968	missense	probably benign	0.00
R7605:Dna2	UTSW	10	62960275	missense	probably benign	0.02
R7742:Dna2	UTSW	10	62973294	missense	probably benign	0.31
R7868:Dna2	UTSW	10	62969864	missense	probably benign	0.00
R7983:Dna2	UTSW	10	62955394	missense	probably benign	0.04
R8498:Dna2	UTSW	10	62973315	missense	probably benign	0.12
R8508:Dna2	UTSW	10	62950894	missense	probably damaging	1.00
R9451:Dna2	UTSW	10	62954293	missense	probably benign	0.00
R9457:Dna2	UTSW	10	62950793	missense	probably benign	0.02
R9571:Dna2	UTSW	10	62964961	missense	probably damaging	1.00
R9772:Dna2	UTSW	10	62950743	missense	probably benign	0.13
RF007:Dna2	UTSW	10	62966695	missense	probably damaging	0.99
Z1177:Dna2	UTSW	10	62962424	missense	probably benign	0.03

Predicted Primers

PCR Primer
(F):5'- TTCAGGCCAAGCGATGGCAGTAAC -3'
(R):5'- GTGTCCAGCAAAGGAAGCCACTAAATC -3'

Sequencing Primer
(F):5'- GCAGTAACAGAAGTTCACCTTG -3'
(R):5'- tgggaggcagaggcagg -3'

Posted On

2014-05-23