Mutagenetix > Incidental Mutation

Incidental Mutation 'R4622:Scn2a'

346207

Institutional Source

Beutler Lab

Gene Symbol

Scn2a

Ensembl Gene

ENSMUSG00000075318

Gene Name

sodium channel, voltage-gated, type II, alpha

Synonyms

A230052E19Rik, Scn2a1, Nav1.2

MMRRC Submission

041887-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4622 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

65620771-65767447 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 65752027 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 1573 (V1573A)

Ref Sequence

ENSEMBL: ENSMUSP00000143882 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028377] [ENSMUST00000100067] [ENSMUST00000200829]

AlphaFold

B1AWN6

Predicted Effect

probably benign
Transcript: ENSMUST00000028377
AA Change: V1573A

PolyPhen 2 Score 0.036 (Sensitivity: 0.94; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000028377
Gene: ENSMUSG00000075318
AA Change: V1573A

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	128	436	2.2e-81	PFAM
low complexity region	450	471	N/A	INTRINSIC
Pfam:Na_trans_cytopl	505	710	9.6e-83	PFAM
Pfam:Ion_trans	759	994	3.6e-57	PFAM
Pfam:Na_trans_assoc	998	1204	1.7e-63	PFAM
Pfam:Ion_trans	1208	1484	3.3e-66	PFAM
Pfam:Ion_trans	1531	1788	2.8e-57	PFAM
Pfam:PKD_channel	1627	1782	8.6e-7	PFAM
IQ	1905	1927	3.59e-3	SMART
low complexity region	1967	1975	N/A	INTRINSIC
low complexity region	1981	2000	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000100067
AA Change: V1573A

PolyPhen 2 Score 0.036 (Sensitivity: 0.94; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000097645
Gene: ENSMUSG00000075318
AA Change: V1573A

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	157	424	3.3e-75	PFAM
low complexity region	433	448	N/A	INTRINSIC
low complexity region	450	471	N/A	INTRINSIC
Pfam:DUF3451	488	711	2.6e-66	PFAM
Pfam:Ion_trans	794	983	1.1e-47	PFAM
Pfam:Na_trans_assoc	998	1219	3.5e-77	PFAM
Pfam:Ion_trans	1245	1473	4.4e-55	PFAM
PDB:1BYY\|A	1475	1527	3e-31	PDB
Pfam:Ion_trans	1566	1776	2.4e-52	PFAM
Pfam:PKD_channel	1628	1783	3.6e-7	PFAM
IQ	1905	1927	3.59e-3	SMART
low complexity region	1967	1975	N/A	INTRINSIC
low complexity region	1981	2000	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000200829
AA Change: V1573A

PolyPhen 2 Score 0.036 (Sensitivity: 0.94; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000143882
Gene: ENSMUSG00000075318
AA Change: V1573A

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	128	436	1.2e-79	PFAM
low complexity region	450	471	N/A	INTRINSIC
Pfam:Na_trans_cytopl	505	710	7.1e-80	PFAM
Pfam:Ion_trans	759	994	2.1e-55	PFAM
Pfam:Na_trans_assoc	998	1204	8e-61	PFAM
Pfam:Ion_trans	1208	1484	1.9e-64	PFAM
Pfam:Ion_trans	1531	1788	1.6e-55	PFAM
Pfam:PKD_channel	1627	1782	1.2e-4	PFAM
IQ	1905	1927	1.8e-5	SMART
low complexity region	1967	1975	N/A	INTRINSIC
low complexity region	1981	2000	N/A	INTRINSIC

Meta Mutation Damage Score

0.1381

Coding Region Coverage

1x: 99.3%
3x: 98.6%
10x: 97.3%
20x: 95.3%

Validation Efficiency

98% (107/109)

MGI Phenotype

FUNCTION: Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with four repeat domains, each of which is composed of six membrane-spanning segments, and one or more regulatory beta subunits. Voltage-gated sodium channels are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. In humans, variants of this gene are associated with seizure disorders and autism spectrum disorder. Mice homozygous for a knockout mutation die with severe hypoxia and extensive neuronal cell death, while gain of function mutations result in progressive seizure disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]
PHENOTYPE: Homozygotes for a targeted mutation exhibit excess neuronal apoptosis (especially in the brainstem), reduced neuronal sodium channel currents in vitro, and severe hypoxia resulting in neonatal lethality. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 99 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1500015O10Rik	G	T	1: 43,742,321	R121L	possibly damaging	Het
2900011O08Rik	A	C	16: 14,093,922	E44A	possibly damaging	Het
Aadacl2	A	T	3: 60,007,053	N26Y	probably damaging	Het
Aass	C	T	6: 23,092,330	D194N	probably damaging	Het
Acp7	T	C	7: 28,614,397	Y404C	probably damaging	Het
Acsl1	A	T	8: 46,526,373	I421L	probably benign	Het
Adgrb3	A	T	1: 25,826,488	D91E	probably damaging	Het
Adgrg3	T	C	8: 95,040,525	S503P	probably damaging	Het
Adgrg6	A	T	10: 14,441,499	C526S	probably damaging	Het
Arhgap32	A	T	9: 32,239,348	I15F	possibly damaging	Het
Arid1b	G	T	17: 4,995,050		probably benign	Het
Asnsd1	A	G	1: 53,348,219	V83A	probably benign	Het
Atg101	A	G	15: 101,293,332		probably benign	Het
Atp8a1	T	C	5: 67,682,713		probably benign	Het
Aurkb	T	A	11: 69,048,362	L137Q	probably damaging	Het
AY702103	A	T	17: 50,240,001		noncoding transcript	Het
B3gnt9	A	G	8: 105,253,845	S304P	probably benign	Het
Babam2	T	C	5: 32,007,312	V310A	probably damaging	Het
Batf	A	G	12: 85,708,553	D60G	possibly damaging	Het
Baz1a	A	T	12: 54,941,515	I283K	probably benign	Het
BC067074	A	G	13: 113,320,081	D887G	probably benign	Het
Bst1	T	G	5: 43,818,919		probably benign	Het
C2	C	A	17: 34,863,674	V490L	probably damaging	Het
Cacna1e	T	C	1: 154,471,565	E952G	possibly damaging	Het
Ccnyl1	A	G	1: 64,718,258	D262G	probably damaging	Het
Cdc42bpa	A	T	1: 180,074,658	K493N	probably damaging	Het
Cenpe	A	G	3: 135,243,708	T85A	probably benign	Het
Ces2e	T	A	8: 104,928,709		probably null	Het
Chd3	T	A	11: 69,349,008	R1665W	probably damaging	Het
Cpm	A	G	10: 117,670,297	N188D	possibly damaging	Het
Ctnnd2	A	T	15: 30,887,169	M781L	probably benign	Het
Ctnnd2	A	G	15: 31,009,113	T1094A	probably benign	Het
Cux1	T	C	5: 136,308,300	K657R	probably damaging	Het
Ddx54	G	A	5: 120,626,423	V732M	probably damaging	Het
Efna5	T	C	17: 62,651,045	D72G	probably benign	Het
Eva1c	T	A	16: 90,897,455		probably null	Het
Evi5l	T	C	8: 4,202,909		probably benign	Het
Fasl	A	G	1: 161,787,134	L120P	probably benign	Het
Gm10334	A	T	6: 41,445,312	I53N	probably damaging	Het
Gm7102	C	T	19: 61,175,926	G24R	unknown	Het
H2-M9	A	T	17: 36,641,824		probably null	Het
Hdgf	C	A	3: 87,914,577	N198K	possibly damaging	Het
Hspa9	A	T	18: 34,949,037	M172K	possibly damaging	Het
Il1r1	A	C	1: 40,312,420	L406F	probably damaging	Het
Il31	T	C	5: 123,480,435	D96G	probably damaging	Het
Inhbc	A	G	10: 127,357,277	I290T	probably benign	Het
Lrp2	A	T	2: 69,460,349	V3589D	possibly damaging	Het
Lrrc14	A	T	15: 76,716,340		probably benign	Het
Lyst	G	A	13: 13,674,398	A2057T	probably benign	Het
Macf1	A	G	4: 123,372,348		probably null	Het
Mapk10	C	A	5: 102,989,724	G209V	probably damaging	Het
Mcoln1	A	G	8: 3,505,923	I73V	probably damaging	Het
Met	G	T	6: 17,513,384	R411L	probably benign	Het
Mkl2	G	A	16: 13,332,706	G102D	probably damaging	Het
Mrpl4	G	A	9: 21,007,497	R176Q	probably damaging	Het
Mtmr3	T	C	11: 4,491,067	T528A	possibly damaging	Het
Mtmr7	A	T	8: 40,581,541	N246K	probably damaging	Het
Mycbp2	G	T	14: 103,219,979	T1627K	probably benign	Het
Necab3	A	G	2: 154,555,582		probably null	Het
Nr1d1	C	T	11: 98,769,884	C419Y	probably damaging	Het
Nwd1	C	A	8: 72,667,300	A397E	probably damaging	Het
Oas1f	A	T	5: 120,848,327	K114N	probably damaging	Het
Olfr1136	T	A	2: 87,693,643	K80*	probably null	Het
Olfr175-ps1	A	T	16: 58,824,106	I201N	possibly damaging	Het
Olfr395	C	A	11: 73,906,911	V194F	possibly damaging	Het
Olfr46	T	A	7: 140,610,698	C169*	probably null	Het
Olfr613	G	T	7: 103,552,154	R123L	probably benign	Het
Osbpl8	T	C	10: 111,291,496	S814P	probably benign	Het
Pcdhgb7	A	T	18: 37,753,130	Q451L	probably benign	Het
Pde7b	C	T	10: 20,418,792	R300Q	probably damaging	Het
Pgghg	A	G	7: 140,941,496		probably null	Het
Plcg1	A	G	2: 160,747,768		probably benign	Het
Plxna2	A	T	1: 194,812,150	I1892L	probably benign	Het
Ppt2	A	G	17: 34,625,901	V123A	probably benign	Het
Prdx5	G	T	19: 6,906,973		probably benign	Het
Prpf40b	A	G	15: 99,316,316	D819G	probably benign	Het
Psap	T	G	10: 60,300,851	C536W	probably damaging	Het
Rab3gap1	T	C	1: 127,942,419	C919R	probably benign	Het
Racgap1	C	A	15: 99,626,206	S440I	probably benign	Het
Rec8	C	T	14: 55,624,758	R480C	probably damaging	Het
Reg3d	A	G	6: 78,377,459	L53S	probably benign	Het
Rnft2	T	A	5: 118,232,406	S244C	probably damaging	Het
Selenoo	G	T	15: 89,095,707	G353*	probably null	Het
Siva1	A	G	12: 112,645,067	Y34C	probably damaging	Het
Slc2a4	C	T	11: 69,944,774		probably benign	Het
Slc39a12	A	T	2: 14,400,325	T243S	probably benign	Het
Slc9b2	T	C	3: 135,332,518	I453T	probably damaging	Het
Spag17	A	G	3: 100,103,243	T2018A	probably benign	Het
Tbc1d24	A	T	17: 24,208,891	D32E	probably benign	Het
Tet1	T	A	10: 62,819,474	H1556L	possibly damaging	Het
Tmem59	A	T	4: 107,190,718		probably benign	Het
Ttn	A	T	2: 76,900,952		probably benign	Het
Uimc1	A	T	13: 55,077,494	L89H	probably damaging	Het
Vipas39	A	G	12: 87,244,543	I343T	probably damaging	Het
Vmn2r71	G	T	7: 85,620,609	V443L	probably benign	Het
Zbtb14	G	A	17: 69,388,347	D347N	possibly damaging	Het
Zfp980	G	T	4: 145,702,057	C452F	probably damaging	Het
Zmym5	T	A	14: 56,812,236		probably benign	Het
Znfx1	T	C	2: 167,041,753	T145A	possibly damaging	Het

Other mutations in Scn2a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00088:Scn2a	APN	2	65764440	missense	probably benign
IGL00159:Scn2a	APN	2	65743090	missense	probably damaging	1.00
IGL00418:Scn2a	APN	2	65764522	missense	probably benign	0.43
IGL00753:Scn2a	APN	2	65683863	missense	possibly damaging	0.66
IGL00770:Scn2a	APN	2	65735853	missense	probably damaging	1.00
IGL00774:Scn2a	APN	2	65735853	missense	probably damaging	1.00
IGL00847:Scn2a	APN	2	65670734	missense	probably damaging	1.00
IGL01155:Scn2a	APN	2	65717748	missense	probably damaging	1.00
IGL01329:Scn2a	APN	2	65717508	missense	probably benign	0.05
IGL01537:Scn2a	APN	2	65715875	missense	probably benign	0.00
IGL01672:Scn2a	APN	2	65751934	missense	probably damaging	1.00
IGL01958:Scn2a	APN	2	65701829	missense	probably damaging	1.00
IGL02028:Scn2a	APN	2	65763658	missense	probably damaging	0.96
IGL02142:Scn2a	APN	2	65715838	missense	probably damaging	1.00
IGL02160:Scn2a	APN	2	65730116	missense	probably damaging	1.00
IGL02183:Scn2a	APN	2	65671603	missense	probably benign	0.20
IGL02341:Scn2a	APN	2	65688377	missense	probably damaging	1.00
IGL02504:Scn2a	APN	2	65683884	missense	probably benign	0.02
IGL02530:Scn2a	APN	2	65730178	missense	probably damaging	0.99
IGL02621:Scn2a	APN	2	65748879	splice site	probably benign
IGL02652:Scn2a	APN	2	65702038	missense	possibly damaging	0.82
IGL02966:Scn2a	APN	2	65701844	missense	possibly damaging	0.93
IGL03188:Scn2a	APN	2	65671653	missense	probably damaging	0.99
IGL03329:Scn2a	APN	2	65764629	missense	probably benign
IGL03336:Scn2a	APN	2	65688744	missense	probably damaging	1.00
IGL03391:Scn2a	APN	2	65764213	missense	probably damaging	1.00
PIT4280001:Scn2a	UTSW	2	65715730	missense	probably damaging	1.00
PIT4362001:Scn2a	UTSW	2	65683838	missense	probably benign	0.09
PIT4403001:Scn2a	UTSW	2	65711908	missense	probably damaging	1.00
PIT4520001:Scn2a	UTSW	2	65688419	missense	probably damaging	1.00
R0021:Scn2a	UTSW	2	65670515	missense	possibly damaging	0.51
R0141:Scn2a	UTSW	2	65711816	missense	probably benign	0.01
R0240:Scn2a	UTSW	2	65735774	missense	probably benign	0.32
R0240:Scn2a	UTSW	2	65735774	missense	probably benign	0.32
R0335:Scn2a	UTSW	2	65682091	missense	probably damaging	1.00
R0508:Scn2a	UTSW	2	65717842	missense	probably damaging	0.99
R0558:Scn2a	UTSW	2	65711925	missense	probably benign	0.26
R0600:Scn2a	UTSW	2	65701833	missense	possibly damaging	0.90
R0667:Scn2a	UTSW	2	65751996	missense	possibly damaging	0.91
R1178:Scn2a	UTSW	2	65686779	splice site	probably benign
R1244:Scn2a	UTSW	2	65763655	missense	probably damaging	0.98
R1386:Scn2a	UTSW	2	65688741	missense	probably damaging	1.00
R1434:Scn2a	UTSW	2	65701991	missense	possibly damaging	0.79
R1440:Scn2a	UTSW	2	65764594	missense	probably benign
R1448:Scn2a	UTSW	2	65683845	missense	probably benign	0.17
R1460:Scn2a	UTSW	2	65701843	missense	probably damaging	0.96
R1553:Scn2a	UTSW	2	65713836	nonsense	probably null
R1642:Scn2a	UTSW	2	65683697	missense	probably damaging	1.00
R1803:Scn2a	UTSW	2	65670767	splice site	probably null
R1981:Scn2a	UTSW	2	65690170	missense	probably damaging	1.00
R2002:Scn2a	UTSW	2	65682083	missense	probably null	1.00
R2068:Scn2a	UTSW	2	65752073	missense	probably benign	0.14
R2125:Scn2a	UTSW	2	65752079	nonsense	probably null
R2126:Scn2a	UTSW	2	65752079	nonsense	probably null
R2876:Scn2a	UTSW	2	65715897	missense	possibly damaging	0.64
R2878:Scn2a	UTSW	2	65688371	missense	probably damaging	1.00
R3113:Scn2a	UTSW	2	65748785	missense	possibly damaging	0.86
R3749:Scn2a	UTSW	2	65713771	missense	probably damaging	1.00
R3750:Scn2a	UTSW	2	65713771	missense	probably damaging	1.00
R3765:Scn2a	UTSW	2	65682710	missense	possibly damaging	0.51
R3850:Scn2a	UTSW	2	65682031	missense	probably benign	0.14
R4585:Scn2a	UTSW	2	65743051	splice site	probably null
R4586:Scn2a	UTSW	2	65743051	splice site	probably null
R4588:Scn2a	UTSW	2	65713767	missense	possibly damaging	0.76
R5108:Scn2a	UTSW	2	65688630	missense	probably damaging	1.00
R5161:Scn2a	UTSW	2	65764591	missense	probably benign	0.00
R5235:Scn2a	UTSW	2	65752011	missense	probably damaging	1.00
R5464:Scn2a	UTSW	2	65701756	missense	probably damaging	1.00
R5586:Scn2a	UTSW	2	65707295	nonsense	probably null
R5630:Scn2a	UTSW	2	65726365	missense	probably damaging	1.00
R5715:Scn2a	UTSW	2	65717584	missense	probably benign	0.27
R5730:Scn2a	UTSW	2	65682538	nonsense	probably null
R5734:Scn2a	UTSW	2	65717722	missense	possibly damaging	0.49
R5779:Scn2a	UTSW	2	65764483	missense	probably benign	0.00
R6133:Scn2a	UTSW	2	65743104	missense	probably benign	0.35
R6547:Scn2a	UTSW	2	65715897	missense	probably benign	0.29
R6549:Scn2a	UTSW	2	65764674	missense	probably benign	0.05
R6818:Scn2a	UTSW	2	65688669	nonsense	probably null
R6999:Scn2a	UTSW	2	65682109	missense	probably benign
R7069:Scn2a	UTSW	2	65764606	missense	probably benign	0.00
R7073:Scn2a	UTSW	2	65728443	missense	probably benign	0.00
R7125:Scn2a	UTSW	2	65763933	missense	probably damaging	1.00
R7178:Scn2a	UTSW	2	65748853	nonsense	probably null
R7179:Scn2a	UTSW	2	65701979	missense	probably damaging	1.00
R7203:Scn2a	UTSW	2	65748319	missense	probably benign	0.01
R7227:Scn2a	UTSW	2	65752023	missense	probably damaging	0.98
R7269:Scn2a	UTSW	2	65763769	missense	probably damaging	1.00
R7358:Scn2a	UTSW	2	65682506	nonsense	probably null
R7388:Scn2a	UTSW	2	65688654	missense	probably damaging	1.00
R7491:Scn2a	UTSW	2	65702008	missense	probably damaging	0.99
R7619:Scn2a	UTSW	2	65715903	missense	probably damaging	1.00
R7695:Scn2a	UTSW	2	65711907	missense	probably damaging	0.99
R7735:Scn2a	UTSW	2	65763669	missense	probably benign	0.40
R7911:Scn2a	UTSW	2	65682083	missense	probably null	1.00
R8096:Scn2a	UTSW	2	65764022	missense	probably damaging	0.98
R8333:Scn2a	UTSW	2	65683847	missense	probably benign	0.01
R8416:Scn2a	UTSW	2	65681001	missense	probably benign	0.00
R8850:Scn2a	UTSW	2	65688386	missense	probably damaging	1.00
R8897:Scn2a	UTSW	2	65715658	critical splice acceptor site	probably null
R8977:Scn2a	UTSW	2	65763670	missense	probably damaging	0.99
R8992:Scn2a	UTSW	2	65763898	missense	probably damaging	1.00
R9190:Scn2a	UTSW	2	65681002	missense	probably benign	0.00
R9206:Scn2a	UTSW	2	65717787	missense	probably damaging	1.00
R9355:Scn2a	UTSW	2	65764089	missense	probably damaging	1.00
R9452:Scn2a	UTSW	2	65764819	missense	probably benign
R9529:Scn2a	UTSW	2	65764588	missense	probably damaging	0.99
R9567:Scn2a	UTSW	2	65688630	missense	probably damaging	1.00
R9569:Scn2a	UTSW	2	65730278	missense	probably damaging	1.00
R9657:Scn2a	UTSW	2	65735688	missense	probably damaging	1.00
R9715:Scn2a	UTSW	2	65748805	missense	possibly damaging	0.93
R9761:Scn2a	UTSW	2	65735686	missense	probably damaging	1.00
Z1176:Scn2a	UTSW	2	65751868	missense	possibly damaging	0.84
Z1177:Scn2a	UTSW	2	65717735	missense	probably benign	0.07

Predicted Primers

PCR Primer
(F):5'- AAAGAGTTTCTGAGTGTACTTGCC -3'
(R):5'- GGAATGGACTATTCGGCTTTATC -3'

Sequencing Primer
(F):5'- GCCTGTGTTATTTATTCCAGAACAAG -3'
(R):5'- CATCCTAAATACAGGGGTTACTAGC -3'

Posted On

2015-09-25