Mutagenetix > Incidental Mutation

Incidental Mutation 'R8039:Cacna2d2'

618422

Institutional Source

Beutler Lab

Gene Symbol

Cacna2d2

Ensembl Gene

ENSMUSG00000010066

Gene Name

calcium channel, voltage-dependent, alpha 2/delta subunit 2

Synonyms

a2d2

MMRRC Submission

067476-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.866) question?

Stock #

R8039 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

107399612-107529343 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 107527433 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Aspartic acid at position 1139 (V1139D)

Ref Sequence

ENSEMBL: ENSMUSP00000010210 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000010210] [ENSMUST00000085092] [ENSMUST00000164988] [ENSMUST00000166799] [ENSMUST00000168532] [ENSMUST00000170737]

AlphaFold

Q6PHS9

Predicted Effect

possibly damaging
Transcript: ENSMUST00000010210
AA Change: V1139D

PolyPhen 2 Score 0.915 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000010210
Gene: ENSMUSG00000010066
AA Change: V1139D

Domain	Start	End	E-Value	Type
low complexity region	20	36	N/A	INTRINSIC
low complexity region	43	57	N/A	INTRINSIC
Pfam:VWA_N	144	268	2e-48	PFAM
VWA	292	467	4.93e-22	SMART
Pfam:Cache_1	488	577	9.9e-32	PFAM
Pfam:VGCC_alpha2	583	673	1.8e-33	PFAM
low complexity region	968	977	N/A	INTRINSIC
low complexity region	1114	1137	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000085092
AA Change: V1145D

PolyPhen 2 Score 0.861 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000082173
Gene: ENSMUSG00000010066
AA Change: V1145D

Domain	Start	End	E-Value	Type
low complexity region	20	36	N/A	INTRINSIC
low complexity region	43	57	N/A	INTRINSIC
Pfam:VWA_N	144	268	2e-48	PFAM
VWA	292	467	4.93e-22	SMART
Pfam:Cache_1	488	577	1e-31	PFAM
Pfam:VGCC_alpha2	583	676	5.8e-35	PFAM
low complexity region	974	983	N/A	INTRINSIC
low complexity region	1120	1143	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000164988
AA Change: V1148D

PolyPhen 2 Score 0.861 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000130451
Gene: ENSMUSG00000010066
AA Change: V1148D

Domain	Start	End	E-Value	Type
low complexity region	20	36	N/A	INTRINSIC
low complexity region	43	57	N/A	INTRINSIC
Pfam:VWA_N	144	268	6.7e-49	PFAM
VWA	292	467	4.93e-22	SMART
Pfam:Cache_1	488	577	2.4e-31	PFAM
Pfam:VGCC_alpha2	583	675	2.5e-34	PFAM
low complexity region	974	983	N/A	INTRINSIC
low complexity region	1123	1146	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000166799
AA Change: V1148D

PolyPhen 2 Score 0.915 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000126029
Gene: ENSMUSG00000010066
AA Change: V1148D

Domain	Start	End	E-Value	Type
low complexity region	20	36	N/A	INTRINSIC
low complexity region	43	57	N/A	INTRINSIC
Pfam:VWA_N	144	268	8.5e-44	PFAM
VWA	292	467	4.93e-22	SMART
Pfam:Cache_1	488	576	1.3e-32	PFAM
Pfam:VGCC_alpha2	583	675	1.4e-47	PFAM
low complexity region	975	984	N/A	INTRINSIC
low complexity region	1123	1146	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000168532
AA Change: V1147D

PolyPhen 2 Score 0.915 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000132512
Gene: ENSMUSG00000010066
AA Change: V1147D

Domain	Start	End	E-Value	Type
low complexity region	20	36	N/A	INTRINSIC
low complexity region	43	57	N/A	INTRINSIC
Pfam:VWA_N	144	268	2.1e-48	PFAM
VWA	292	467	4.93e-22	SMART
Pfam:Cache_1	488	577	1e-31	PFAM
Pfam:VGCC_alpha2	583	676	5.8e-35	PFAM
low complexity region	974	983	N/A	INTRINSIC
low complexity region	1122	1145	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000170737
AA Change: V1141D

PolyPhen 2 Score 0.915 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000125943
Gene: ENSMUSG00000010066
AA Change: V1141D

Domain	Start	End	E-Value	Type
low complexity region	20	36	N/A	INTRINSIC
low complexity region	43	57	N/A	INTRINSIC
Pfam:VWA_N	144	268	2e-48	PFAM
VWA	292	467	4.93e-22	SMART
Pfam:Cache_1	488	577	1e-31	PFAM
Pfam:VGCC_alpha2	583	673	1.9e-33	PFAM
low complexity region	968	977	N/A	INTRINSIC
low complexity region	1116	1139	N/A	INTRINSIC

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.5%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Calcium channels mediate the entry of calcium ions into the cell upon membrane polarization. This gene encodes the alpha-2/delta subunit of the voltage-dependent calcium channel complex. The complex consists of the main channel-forming subunit alpha-1, and auxiliary subunits alpha-2/delta, beta, and gamma. The auxiliary subunits function in the assembly and membrane localization of the complex, and modulate calcium currents and channel activation/inactivation kinetics. The subunit encoded by this gene undergoes post-translational cleavage to yield the extracellular alpha2 peptide and a membrane-anchored delta polypeptide. This subunit is a receptor for the antiepileptic drug, gabapentin. Mutations in this gene are associated with early infantile epileptic encephalopathy. Single nucleotide polymorphisms in this gene are correlated with increased sensitivity to opioid drugs. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]
PHENOTYPE: Homozygotes for different mutant alleles show variable movement abnormalities including waddling, reeling or very slow gait, ataxia, and mild spike-wave seizures. While gross CNS abnormalities and demyelination are present in some mutant lines, they are not observed in others. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 86 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4932438A13Rik	T	A	3: 36,943,214	V1140E	probably benign	Het
Abca17	T	C	17: 24,328,725	H225R	probably damaging	Het
Adgrb2	T	A	4: 130,022,268	L1451Q	probably damaging	Het
Afdn	T	C	17: 13,899,141	L1713P	probably damaging	Het
Agr2	A	T	12: 35,995,559	I15F	probably benign	Het
Agrn	T	C	4: 156,169,011	T1808A	probably benign	Het
Akap6	A	G	12: 53,141,676	I1958V	probably benign	Het
Ankrd60	C	A	2: 173,572,491		probably null	Het
Anpep	A	G	7: 79,839,400		probably null	Het
Apoa4	A	T	9: 46,242,293	D64V	possibly damaging	Het
Arhgef26	C	A	3: 62,339,930	T145N	probably benign	Het
Art1	A	T	7: 102,106,845	Q81L	probably benign	Het
Astl	A	T	2: 127,343,983	S71C	probably damaging	Het
Atp2a1	A	G	7: 126,448,805	I611T	probably damaging	Het
Chst10	T	A	1: 38,866,031	K198*	probably null	Het
Ckmt2	G	A	13: 91,863,312	H60Y	possibly damaging	Het
Coq7	G	C	7: 118,533,246	S2R	possibly damaging	Het
Cspp1	T	A	1: 10,113,013	D814E	probably benign	Het
Cyp2c54	CCTCTTTCATAGCTCT	CCTCT	19: 40,073,732		probably null	Het
Daam2	C	A	17: 49,464,538	G860V	probably damaging	Het
Ecm2	A	T	13: 49,514,850	I10F	probably benign	Het
Epb41l1	A	T	2: 156,506,412	D312V	probably damaging	Het
Epsti1	G	A	14: 77,931,301	R126H	probably damaging	Het
Erc1	A	T	6: 119,773,665	Y367*	probably null	Het
Erh	T	A	12: 80,637,578	R42W	probably damaging	Het
Fam124a	C	T	14: 62,605,876	Q278*	probably null	Het
Fam155a	T	C	8: 9,207,892	T419A	probably benign	Het
Fbxo3	T	A	2: 104,054,941	L385Q	probably damaging	Het
Fbxo31	T	A	8: 121,559,055	T219S	probably damaging	Het
Fstl5	T	G	3: 76,648,418	V534G	possibly damaging	Het
Gatsl3	G	T	11: 4,221,639	A288S	probably damaging	Het
Gbp2b	A	T	3: 142,618,164	I577F	probably benign	Het
Gbp8	A	T	5: 105,050,917	L44*	probably null	Het
Gck	C	T	11: 5,910,301	A114T	probably benign	Het
Gm16486	T	C	8: 70,710,906	V916A	probably benign	Het
Gtf2i	A	G	5: 134,255,834	V537A	possibly damaging	Het
Iqcm	C	A	8: 75,763,105	H400Q	probably damaging	Het
Itpr1	T	C	6: 108,386,628	L737P	probably damaging	Het
Jakmip1	A	G	5: 37,100,772	E254G	probably damaging	Het
Kif15	A	T	9: 123,007,425	R1095W	possibly damaging	Het
Klhdc8a	G	A	1: 132,303,108	R237Q	probably benign	Het
Klhl38	T	C	15: 58,322,862	E157G	probably benign	Het
Klrk1	T	A	6: 129,612,823	N221I	probably benign	Het
Lhx8	A	T	3: 154,306,939	H345Q	probably damaging	Het
Lims1	T	A	10: 58,409,672	N174K	probably benign	Het
Madd	T	A	2: 91,167,061	Q754L	probably benign	Het
Mau2	T	C	8: 70,019,790	D581G	probably damaging	Het
Miga1	A	T	3: 152,276,756	I561N	probably benign	Het
Mmp1a	TG	TGG	9: 7,465,083		probably null	Het
Mob3c	T	C	4: 115,831,687	V139A	probably benign	Het
Nadk	G	T	4: 155,577,067	D17Y	probably benign	Het
Ncapd2	C	T	6: 125,181,026	V380I	probably damaging	Het
Nes	G	A	3: 87,977,008	R858K	probably benign	Het
Nphp3	T	C	9: 104,031,963	S791P	probably benign	Het
Nup210	T	C	6: 91,070,233	T496A	probably benign	Het
Ogfr	GGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGGGCCAGAGGACCCCCAAAGCCAGGTGG	GGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGGGCCAGAGGACCCCCAAAGCCAGGTGG	2: 180,595,266		probably benign	Het
Olfr1186	C	T	2: 88,525,871	T96I	probably benign	Het
Olfr220	T	A	1: 174,449,596	S324R	unknown	Het
Olfr914	T	A	9: 38,607,389	M308K	probably benign	Het
Ovgp1	T	A	3: 105,976,023	S105T	probably benign	Het
Pbld2	T	A	10: 63,047,992	C79S	probably damaging	Het
Pik3cd	T	A	4: 149,659,866	M143L	possibly damaging	Het
Plat	G	T	8: 22,772,232	G91W	probably damaging	Het
Poln	A	G	5: 34,122,672	V282A	probably benign	Het
Ppp1r11	T	C	17: 36,951,446	T21A	probably damaging	Het
Prpf8	T	A	11: 75,502,542	I1664N	possibly damaging	Het
Prr29	C	T	11: 106,376,912	A161V	probably benign	Het
Rasa3	T	C	8: 13,588,931	D292G	probably damaging	Het
Rnf25	T	C	1: 74,593,964	T411A	probably damaging	Het
Rraga	C	T	4: 86,575,980	T21I	probably damaging	Het
Setdb2	T	A	14: 59,402,375	Y673F	probably damaging	Het
Sf3a1	C	T	11: 4,167,787	T183I	probably damaging	Het
Shank3	A	T	15: 89,505,439	H413L	probably damaging	Het
Slc30a5	A	G	13: 100,813,681		probably null	Het
Slc6a18	T	C	13: 73,665,626	S523G	probably benign	Het
Spaca1	C	T	4: 34,044,207	V96I	probably damaging	Het
Sycp2	C	T	2: 178,374,585	A695T	probably benign	Het
Tnrc18	C	A	5: 142,732,052	G2216C	unknown	Het
Trak2	T	C	1: 58,946,288	N17S	probably benign	Het
Ttn	T	A	2: 76,878,432	N8792I	unknown	Het
Ttyh1	T	C	7: 4,122,541	V64A	probably benign	Het
Usb1	T	A	8: 95,333,413	S50R	probably damaging	Het
Ush2a	T	A	1: 188,957,373	I5044N	probably damaging	Het
Vmn1r84	A	T	7: 12,362,008	F253I	possibly damaging	Het
Vmn2r99	T	C	17: 19,380,040	I442T	probably benign	Het
Vsig1	C	T	X: 140,933,126	H232Y	probably benign	Het

Other mutations in Cacna2d2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00401:Cacna2d2	APN	9	107514873	missense	probably damaging	1.00
IGL00425:Cacna2d2	APN	9	107527351	missense	probably damaging	1.00
IGL01294:Cacna2d2	APN	9	107514081	missense	probably damaging	1.00
IGL01969:Cacna2d2	APN	9	107509216	missense	probably benign
IGL01974:Cacna2d2	APN	9	107517422	missense	probably benign	0.00
IGL02001:Cacna2d2	APN	9	107522116	missense	probably benign
IGL02125:Cacna2d2	APN	9	107513904	nonsense	probably null
IGL02143:Cacna2d2	APN	9	107518275	splice site	probably null
IGL02150:Cacna2d2	APN	9	107527316	splice site	probably benign
IGL02213:Cacna2d2	APN	9	107514048	missense	probably damaging	1.00
IGL02220:Cacna2d2	APN	9	107514879	missense	probably damaging	1.00
IGL02238:Cacna2d2	APN	9	107513558	missense	probably damaging	0.99
IGL02466:Cacna2d2	APN	9	107465554	missense	probably damaging	1.00
IGL02569:Cacna2d2	APN	9	107514046	missense	probably damaging	0.99
IGL02571:Cacna2d2	APN	9	107525646	missense	possibly damaging	0.93
IGL02825:Cacna2d2	APN	9	107524460	missense	probably damaging	1.00
IGL03000:Cacna2d2	APN	9	107524198	splice site	probably null
IGL03064:Cacna2d2	APN	9	107509275	missense	probably damaging	1.00
Blow	UTSW	9	107513606	missense	probably null	0.90
dilemma	UTSW	9	107514864	missense	probably damaging	1.00
hera	UTSW	9	107513280	missense	probably damaging	1.00
Ionian	UTSW	9	107525376	missense	probably benign	0.05
Solomonic	UTSW	9	107524662	missense	possibly damaging	0.94
PIT4131001:Cacna2d2	UTSW	9	107524668	missense	probably damaging	1.00
R0233:Cacna2d2	UTSW	9	107514670	missense	probably damaging	0.96
R0233:Cacna2d2	UTSW	9	107514670	missense	probably damaging	0.96
R0387:Cacna2d2	UTSW	9	107513881	missense	probably damaging	1.00
R0410:Cacna2d2	UTSW	9	107524620	missense	probably damaging	1.00
R0538:Cacna2d2	UTSW	9	107524383	splice site	probably benign
R0545:Cacna2d2	UTSW	9	107525223	missense	probably damaging	1.00
R0729:Cacna2d2	UTSW	9	107517257	missense	probably benign	0.06
R1024:Cacna2d2	UTSW	9	107527050	critical splice donor site	probably null
R1538:Cacna2d2	UTSW	9	107517416	missense	probably damaging	1.00
R1750:Cacna2d2	UTSW	9	107524644	missense	probably damaging	1.00
R1774:Cacna2d2	UTSW	9	107526151	missense	probably benign	0.19
R1800:Cacna2d2	UTSW	9	107527433	missense	possibly damaging	0.46
R1873:Cacna2d2	UTSW	9	107513872	missense	probably damaging	0.98
R1935:Cacna2d2	UTSW	9	107509256	missense	probably damaging	1.00
R1936:Cacna2d2	UTSW	9	107509256	missense	probably damaging	1.00
R1971:Cacna2d2	UTSW	9	107512006	missense	probably damaging	0.98
R2095:Cacna2d2	UTSW	9	107527165	missense	probably benign	0.05
R2135:Cacna2d2	UTSW	9	107526513	missense	possibly damaging	0.74
R2197:Cacna2d2	UTSW	9	107527403	missense	probably damaging	0.97
R2266:Cacna2d2	UTSW	9	107513280	missense	probably damaging	1.00
R2483:Cacna2d2	UTSW	9	107512022	missense	probably damaging	1.00
R4021:Cacna2d2	UTSW	9	107514058	missense	probably damaging	1.00
R4392:Cacna2d2	UTSW	9	107400280	missense	possibly damaging	0.47
R4629:Cacna2d2	UTSW	9	107527322	missense	probably damaging	1.00
R5053:Cacna2d2	UTSW	9	107514864	missense	probably damaging	1.00
R5327:Cacna2d2	UTSW	9	107513606	missense	probably null	0.90
R5347:Cacna2d2	UTSW	9	107514114	missense	probably benign
R5719:Cacna2d2	UTSW	9	107524652	missense	probably benign	0.36
R5737:Cacna2d2	UTSW	9	107526747	missense	possibly damaging	0.70
R5739:Cacna2d2	UTSW	9	107512329	missense	probably benign	0.37
R6037:Cacna2d2	UTSW	9	107513539	missense	probably damaging	1.00
R6037:Cacna2d2	UTSW	9	107513539	missense	probably damaging	1.00
R6084:Cacna2d2	UTSW	9	107497521	critical splice donor site	probably null
R6170:Cacna2d2	UTSW	9	107527334	missense	probably damaging	1.00
R6254:Cacna2d2	UTSW	9	107509216	missense	probably benign
R6427:Cacna2d2	UTSW	9	107515442	missense	possibly damaging	0.67
R7652:Cacna2d2	UTSW	9	107524198	splice site	probably null
R7850:Cacna2d2	UTSW	9	107525376	missense	probably benign	0.05
R7936:Cacna2d2	UTSW	9	107524127	missense	probably damaging	1.00
R7978:Cacna2d2	UTSW	9	107518257	missense	probably benign	0.14
R8165:Cacna2d2	UTSW	9	107525454	splice site	probably null
R8274:Cacna2d2	UTSW	9	107524662	missense	possibly damaging	0.94
R8286:Cacna2d2	UTSW	9	107514864	missense	probably damaging	1.00
R8354:Cacna2d2	UTSW	9	107524135	missense	possibly damaging	0.95
R8464:Cacna2d2	UTSW	9	107512007	missense	probably damaging	0.99
R8479:Cacna2d2	UTSW	9	107526397	critical splice donor site	probably null
R8765:Cacna2d2	UTSW	9	107517159	missense	probably damaging	1.00
R8848:Cacna2d2	UTSW	9	107514656	missense	possibly damaging	0.75
R9037:Cacna2d2	UTSW	9	107509196	missense	probably benign	0.08
R9225:Cacna2d2	UTSW	9	107526204	missense	probably benign	0.10
R9295:Cacna2d2	UTSW	9	107509220	missense	probably benign	0.02
R9372:Cacna2d2	UTSW	9	107517603	missense	probably benign	0.00
R9414:Cacna2d2	UTSW	9	107515196	missense	probably damaging	1.00
R9417:Cacna2d2	UTSW	9	107515490	nonsense	probably null
R9435:Cacna2d2	UTSW	9	107519185	missense	probably benign	0.01
R9584:Cacna2d2	UTSW	9	107400205	missense	probably damaging	0.97
R9642:Cacna2d2	UTSW	9	107515428	missense	possibly damaging	0.94
R9784:Cacna2d2	UTSW	9	107527147	missense	probably benign	0.00
Z1176:Cacna2d2	UTSW	9	107517293	missense	probably damaging	1.00
Z1176:Cacna2d2	UTSW	9	107526102	missense	probably benign	0.14

Predicted Primers

PCR Primer
(F):5'- TACTGACATCTGCGAGCCTG -3'
(R):5'- GAGCTAAATCTTGAGTGCCAAAC -3'

Sequencing Primer
(F):5'- TGAGCCGGGTGGATACC -3'
(R):5'- ACCATGGCACCTTACTTTGGGG -3'

Posted On

2020-01-23