Mutagenetix > Incidental Mutation

Incidental Mutation 'R3850:Scn2a'

275853

Institutional Source

Beutler Lab

Gene Symbol

Scn2a

Ensembl Gene

ENSMUSG00000075318

Gene Name

sodium channel, voltage-gated, type II, alpha

Synonyms

A230052E19Rik, Nav1.2, Scn2a1

MMRRC Submission

040898-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R3850 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

65451115-65597791 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 65512375 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Phenylalanine at position 171 (L171F)

Ref Sequence

ENSEMBL: ENSMUSP00000117955 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028377] [ENSMUST00000100067] [ENSMUST00000144254] [ENSMUST00000200829]

AlphaFold

B1AWN6

Predicted Effect

probably benign
Transcript: ENSMUST00000028377
AA Change: L171F

PolyPhen 2 Score 0.030 (Sensitivity: 0.95; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000028377
Gene: ENSMUSG00000075318
AA Change: L171F

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: L171F

PolyPhen 2 Score 0.030 (Sensitivity: 0.95; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000097645
Gene: ENSMUSG00000075318
AA Change: L171F

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

noncoding transcript
Transcript: ENSMUST00000138368

Predicted Effect

probably benign
Transcript: ENSMUST00000144254
AA Change: L171F

PolyPhen 2 Score 0.138 (Sensitivity: 0.92; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000117955
Gene: ENSMUSG00000075318
AA Change: L171F

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	128	436	7.2e-81	PFAM
low complexity region	450	471	N/A	INTRINSIC
low complexity region	484	502	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000200829
AA Change: L171F

PolyPhen 2 Score 0.030 (Sensitivity: 0.95; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000143882
Gene: ENSMUSG00000075318
AA Change: L171F

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

0.3685

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.6%
20x: 96.0%

Validation Efficiency

100% (59/59)

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: 57 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca1	C	T	4: 53,061,481 (GRCm39)		probably benign	Het
Abcc5	A	T	16: 20,190,906 (GRCm39)	S815T	probably benign	Het
Adamts17	T	A	7: 66,490,215 (GRCm39)	L99Q	possibly damaging	Het
Adamtsl1	A	T	4: 86,336,783 (GRCm39)	Q1564L	probably damaging	Het
Als2cl	A	G	9: 110,718,377 (GRCm39)		probably benign	Het
Antxrl	C	A	14: 33,789,338 (GRCm39)	H309Q	probably benign	Het
Ap1g2	T	C	14: 55,342,363 (GRCm39)	M165V	probably benign	Het
Cacna2d3	A	G	14: 29,069,077 (GRCm39)		probably null	Het
Cdh16	T	C	8: 105,344,473 (GRCm39)	D22G	possibly damaging	Het
Cdh17	A	G	4: 11,785,201 (GRCm39)	D331G	probably damaging	Het
Csmd1	C	G	8: 16,129,936 (GRCm39)	V1729L	probably benign	Het
Cul5	T	G	9: 53,529,286 (GRCm39)	M800L	probably benign	Het
Cwf19l1	T	C	19: 44,119,937 (GRCm39)	Y68C	probably benign	Het
Dst	C	T	1: 34,228,355 (GRCm39)	Q1658*	probably null	Het
Dst	C	T	1: 34,251,400 (GRCm39)	S4165F	probably damaging	Het
Fan1	T	C	7: 64,022,119 (GRCm39)	Y378C	probably damaging	Het
Fat4	T	A	3: 39,061,410 (GRCm39)	V4331D	probably benign	Het
Fbxl8	T	C	8: 105,993,781 (GRCm39)	S46P	probably benign	Het
Golgb1	C	A	16: 36,719,095 (GRCm39)	Q334K	probably benign	Het
Hoxc10	T	C	15: 102,875,879 (GRCm39)	V196A	probably benign	Het
Hsf4	T	C	8: 105,997,469 (GRCm39)	F101L	probably damaging	Het
Hydin	T	C	8: 111,290,561 (GRCm39)	I3340T	probably damaging	Het
Igfbpl1	C	T	4: 45,826,426 (GRCm39)	R123H	probably benign	Het
Mov10l1	A	T	15: 88,889,898 (GRCm39)		probably null	Het
Mrc2	T	C	11: 105,183,729 (GRCm39)		probably null	Het
Muc5b	G	A	7: 141,416,375 (GRCm39)	C3107Y	possibly damaging	Het
Naip2	A	T	13: 100,315,940 (GRCm39)	L280Q	probably damaging	Het
Naip2	G	C	13: 100,315,941 (GRCm39)	L280V	probably damaging	Het
Nek1	T	A	8: 61,525,349 (GRCm39)	F596I	probably damaging	Het
Nfasc	T	C	1: 132,559,471 (GRCm39)	T214A	probably damaging	Het
Or4a72	T	C	2: 89,405,378 (GRCm39)	R231G	probably damaging	Het
Or5aq1b	T	A	2: 86,902,310 (GRCm39)	H56L	possibly damaging	Het
Or7d10	A	T	9: 19,832,105 (GRCm39)	Y200F	probably damaging	Het
Pcdhga10	C	T	18: 37,882,074 (GRCm39)	P612S	probably damaging	Het
Picalm	A	G	7: 89,840,912 (GRCm39)	N456S	probably damaging	Het
Pigo	A	G	4: 43,025,084 (GRCm39)	F5S	probably benign	Het
Pikfyve	T	C	1: 65,270,004 (GRCm39)	F563S	probably damaging	Het
Plod2	A	G	9: 92,424,598 (GRCm39)	E29G	probably benign	Het
Pm20d2	A	G	4: 33,174,414 (GRCm39)	V403A	probably damaging	Het
Proz	A	G	8: 13,123,533 (GRCm39)	E268G	probably benign	Het
Rb1cc1	T	A	1: 6,320,337 (GRCm39)	V1252D	probably benign	Het
Rimbp3	A	T	16: 17,028,163 (GRCm39)	H529L	probably benign	Het
Rmdn3	A	T	2: 118,986,903 (GRCm39)	H41Q	possibly damaging	Het
Rnf17	T	C	14: 56,749,753 (GRCm39)	V1433A	probably damaging	Het
Ror1	A	G	4: 100,299,357 (GRCm39)	Y910C	possibly damaging	Het
Sh3pxd2b	A	G	11: 32,361,505 (GRCm39)	E239G	probably damaging	Het
Smim33	G	A	18: 35,861,767 (GRCm39)	V84I	probably benign	Het
Snx27	G	T	3: 94,427,542 (GRCm39)	T311K	probably benign	Het
Sspo	T	A	6: 48,469,424 (GRCm39)	L4459Q	probably damaging	Het
Syne2	T	C	12: 76,095,396 (GRCm39)	L5241P	probably damaging	Het
Tas2r110	T	A	6: 132,845,638 (GRCm39)	I223N	probably damaging	Het
Tead2	T	A	7: 44,881,752 (GRCm39)		probably null	Het
Thap12	G	T	7: 98,365,870 (GRCm39)	K679N	probably damaging	Het
Vmn2r65	T	A	7: 84,595,859 (GRCm39)	H275L	probably benign	Het
Wfs1	C	A	5: 37,125,968 (GRCm39)	V308L	probably benign	Het
Zfp229	C	A	17: 21,964,843 (GRCm39)	H358N	probably damaging	Het
Zfp687	T	C	3: 94,915,225 (GRCm39)	D1092G	probably damaging	Het

Other mutations in Scn2a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00088:Scn2a	APN	2	65,594,784 (GRCm39)	missense	probably benign
IGL00159:Scn2a	APN	2	65,573,434 (GRCm39)	missense	probably damaging	1.00
IGL00418:Scn2a	APN	2	65,594,866 (GRCm39)	missense	probably benign	0.43
IGL00753:Scn2a	APN	2	65,514,207 (GRCm39)	missense	possibly damaging	0.66
IGL00770:Scn2a	APN	2	65,566,197 (GRCm39)	missense	probably damaging	1.00
IGL00774:Scn2a	APN	2	65,566,197 (GRCm39)	missense	probably damaging	1.00
IGL00847:Scn2a	APN	2	65,501,078 (GRCm39)	missense	probably damaging	1.00
IGL01155:Scn2a	APN	2	65,548,092 (GRCm39)	missense	probably damaging	1.00
IGL01329:Scn2a	APN	2	65,547,852 (GRCm39)	missense	probably benign	0.05
IGL01537:Scn2a	APN	2	65,546,219 (GRCm39)	missense	probably benign	0.00
IGL01672:Scn2a	APN	2	65,582,278 (GRCm39)	missense	probably damaging	1.00
IGL01958:Scn2a	APN	2	65,532,173 (GRCm39)	missense	probably damaging	1.00
IGL02028:Scn2a	APN	2	65,594,002 (GRCm39)	missense	probably damaging	0.96
IGL02142:Scn2a	APN	2	65,546,182 (GRCm39)	missense	probably damaging	1.00
IGL02160:Scn2a	APN	2	65,560,460 (GRCm39)	missense	probably damaging	1.00
IGL02183:Scn2a	APN	2	65,501,947 (GRCm39)	missense	probably benign	0.20
IGL02341:Scn2a	APN	2	65,518,721 (GRCm39)	missense	probably damaging	1.00
IGL02504:Scn2a	APN	2	65,514,228 (GRCm39)	missense	probably benign	0.02
IGL02530:Scn2a	APN	2	65,560,522 (GRCm39)	missense	probably damaging	0.99
IGL02621:Scn2a	APN	2	65,579,223 (GRCm39)	splice site	probably benign
IGL02652:Scn2a	APN	2	65,532,382 (GRCm39)	missense	possibly damaging	0.82
IGL02966:Scn2a	APN	2	65,532,188 (GRCm39)	missense	possibly damaging	0.93
IGL03188:Scn2a	APN	2	65,501,997 (GRCm39)	missense	probably damaging	0.99
IGL03329:Scn2a	APN	2	65,594,973 (GRCm39)	missense	probably benign
IGL03336:Scn2a	APN	2	65,519,088 (GRCm39)	missense	probably damaging	1.00
IGL03391:Scn2a	APN	2	65,594,557 (GRCm39)	missense	probably damaging	1.00
PIT4280001:Scn2a	UTSW	2	65,546,074 (GRCm39)	missense	probably damaging	1.00
PIT4362001:Scn2a	UTSW	2	65,514,182 (GRCm39)	missense	probably benign	0.09
PIT4403001:Scn2a	UTSW	2	65,542,252 (GRCm39)	missense	probably damaging	1.00
PIT4520001:Scn2a	UTSW	2	65,518,763 (GRCm39)	missense	probably damaging	1.00
R0021:Scn2a	UTSW	2	65,500,859 (GRCm39)	missense	possibly damaging	0.51
R0141:Scn2a	UTSW	2	65,542,160 (GRCm39)	missense	probably benign	0.01
R0240:Scn2a	UTSW	2	65,566,118 (GRCm39)	missense	probably benign	0.32
R0240:Scn2a	UTSW	2	65,566,118 (GRCm39)	missense	probably benign	0.32
R0335:Scn2a	UTSW	2	65,512,435 (GRCm39)	missense	probably damaging	1.00
R0508:Scn2a	UTSW	2	65,548,186 (GRCm39)	missense	probably damaging	0.99
R0558:Scn2a	UTSW	2	65,542,269 (GRCm39)	missense	probably benign	0.26
R0600:Scn2a	UTSW	2	65,532,177 (GRCm39)	missense	possibly damaging	0.90
R0667:Scn2a	UTSW	2	65,582,340 (GRCm39)	missense	possibly damaging	0.91
R1178:Scn2a	UTSW	2	65,517,123 (GRCm39)	splice site	probably benign
R1244:Scn2a	UTSW	2	65,593,999 (GRCm39)	missense	probably damaging	0.98
R1386:Scn2a	UTSW	2	65,519,085 (GRCm39)	missense	probably damaging	1.00
R1434:Scn2a	UTSW	2	65,532,335 (GRCm39)	missense	possibly damaging	0.79
R1440:Scn2a	UTSW	2	65,594,938 (GRCm39)	missense	probably benign
R1448:Scn2a	UTSW	2	65,514,189 (GRCm39)	missense	probably benign	0.17
R1460:Scn2a	UTSW	2	65,532,187 (GRCm39)	missense	probably damaging	0.96
R1553:Scn2a	UTSW	2	65,544,180 (GRCm39)	nonsense	probably null
R1642:Scn2a	UTSW	2	65,514,041 (GRCm39)	missense	probably damaging	1.00
R1803:Scn2a	UTSW	2	65,501,111 (GRCm39)	splice site	probably null
R1981:Scn2a	UTSW	2	65,520,514 (GRCm39)	missense	probably damaging	1.00
R2002:Scn2a	UTSW	2	65,512,427 (GRCm39)	missense	probably null	1.00
R2068:Scn2a	UTSW	2	65,582,417 (GRCm39)	missense	probably benign	0.14
R2125:Scn2a	UTSW	2	65,582,423 (GRCm39)	nonsense	probably null
R2126:Scn2a	UTSW	2	65,582,423 (GRCm39)	nonsense	probably null
R2876:Scn2a	UTSW	2	65,546,241 (GRCm39)	missense	possibly damaging	0.64
R2878:Scn2a	UTSW	2	65,518,715 (GRCm39)	missense	probably damaging	1.00
R3113:Scn2a	UTSW	2	65,579,129 (GRCm39)	missense	possibly damaging	0.86
R3749:Scn2a	UTSW	2	65,544,115 (GRCm39)	missense	probably damaging	1.00
R3750:Scn2a	UTSW	2	65,544,115 (GRCm39)	missense	probably damaging	1.00
R3765:Scn2a	UTSW	2	65,513,054 (GRCm39)	missense	possibly damaging	0.51
R4585:Scn2a	UTSW	2	65,573,395 (GRCm39)	splice site	probably null
R4586:Scn2a	UTSW	2	65,573,395 (GRCm39)	splice site	probably null
R4588:Scn2a	UTSW	2	65,544,111 (GRCm39)	missense	possibly damaging	0.76
R4622:Scn2a	UTSW	2	65,582,371 (GRCm39)	missense	probably benign	0.04
R5108:Scn2a	UTSW	2	65,518,974 (GRCm39)	missense	probably damaging	1.00
R5161:Scn2a	UTSW	2	65,594,935 (GRCm39)	missense	probably benign	0.00
R5235:Scn2a	UTSW	2	65,582,355 (GRCm39)	missense	probably damaging	1.00
R5464:Scn2a	UTSW	2	65,532,100 (GRCm39)	missense	probably damaging	1.00
R5586:Scn2a	UTSW	2	65,537,639 (GRCm39)	nonsense	probably null
R5630:Scn2a	UTSW	2	65,556,709 (GRCm39)	missense	probably damaging	1.00
R5715:Scn2a	UTSW	2	65,547,928 (GRCm39)	missense	probably benign	0.27
R5730:Scn2a	UTSW	2	65,512,882 (GRCm39)	nonsense	probably null
R5734:Scn2a	UTSW	2	65,548,066 (GRCm39)	missense	possibly damaging	0.49
R5779:Scn2a	UTSW	2	65,594,827 (GRCm39)	missense	probably benign	0.00
R6133:Scn2a	UTSW	2	65,573,448 (GRCm39)	missense	probably benign	0.35
R6547:Scn2a	UTSW	2	65,546,241 (GRCm39)	missense	probably benign	0.29
R6549:Scn2a	UTSW	2	65,595,018 (GRCm39)	missense	probably benign	0.05
R6818:Scn2a	UTSW	2	65,519,013 (GRCm39)	nonsense	probably null
R6999:Scn2a	UTSW	2	65,512,453 (GRCm39)	missense	probably benign
R7069:Scn2a	UTSW	2	65,594,950 (GRCm39)	missense	probably benign	0.00
R7073:Scn2a	UTSW	2	65,558,787 (GRCm39)	missense	probably benign	0.00
R7125:Scn2a	UTSW	2	65,594,277 (GRCm39)	missense	probably damaging	1.00
R7178:Scn2a	UTSW	2	65,579,197 (GRCm39)	nonsense	probably null
R7179:Scn2a	UTSW	2	65,532,323 (GRCm39)	missense	probably damaging	1.00
R7203:Scn2a	UTSW	2	65,578,663 (GRCm39)	missense	probably benign	0.01
R7227:Scn2a	UTSW	2	65,582,367 (GRCm39)	missense	probably damaging	0.98
R7269:Scn2a	UTSW	2	65,594,113 (GRCm39)	missense	probably damaging	1.00
R7358:Scn2a	UTSW	2	65,512,850 (GRCm39)	nonsense	probably null
R7388:Scn2a	UTSW	2	65,518,998 (GRCm39)	missense	probably damaging	1.00
R7491:Scn2a	UTSW	2	65,532,352 (GRCm39)	missense	probably damaging	0.99
R7619:Scn2a	UTSW	2	65,546,247 (GRCm39)	missense	probably damaging	1.00
R7695:Scn2a	UTSW	2	65,542,251 (GRCm39)	missense	probably damaging	0.99
R7735:Scn2a	UTSW	2	65,594,013 (GRCm39)	missense	probably benign	0.40
R7911:Scn2a	UTSW	2	65,512,427 (GRCm39)	missense	probably null	1.00
R8096:Scn2a	UTSW	2	65,594,366 (GRCm39)	missense	probably damaging	0.98
R8172:Scn2a	UTSW	2	65,520,672 (GRCm39)	missense	probably benign	0.01
R8220:Scn2a	UTSW	2	65,520,620 (GRCm39)	missense	probably benign	0.01
R8333:Scn2a	UTSW	2	65,514,191 (GRCm39)	missense	probably benign	0.01
R8416:Scn2a	UTSW	2	65,511,345 (GRCm39)	missense	probably benign	0.00
R8850:Scn2a	UTSW	2	65,518,730 (GRCm39)	missense	probably damaging	1.00
R8897:Scn2a	UTSW	2	65,546,002 (GRCm39)	critical splice acceptor site	probably null
R8977:Scn2a	UTSW	2	65,594,014 (GRCm39)	missense	probably damaging	0.99
R8992:Scn2a	UTSW	2	65,594,242 (GRCm39)	missense	probably damaging	1.00
R9190:Scn2a	UTSW	2	65,511,346 (GRCm39)	missense	probably benign	0.00
R9206:Scn2a	UTSW	2	65,548,131 (GRCm39)	missense	probably damaging	1.00
R9355:Scn2a	UTSW	2	65,594,433 (GRCm39)	missense	probably damaging	1.00
R9452:Scn2a	UTSW	2	65,595,163 (GRCm39)	missense	probably benign
R9529:Scn2a	UTSW	2	65,594,932 (GRCm39)	missense	probably damaging	0.99
R9567:Scn2a	UTSW	2	65,518,974 (GRCm39)	missense	probably damaging	1.00
R9569:Scn2a	UTSW	2	65,560,622 (GRCm39)	missense	probably damaging	1.00
R9657:Scn2a	UTSW	2	65,566,032 (GRCm39)	missense	probably damaging	1.00
R9715:Scn2a	UTSW	2	65,579,149 (GRCm39)	missense	possibly damaging	0.93
R9761:Scn2a	UTSW	2	65,566,030 (GRCm39)	missense	probably damaging	1.00
Z1176:Scn2a	UTSW	2	65,582,212 (GRCm39)	missense	possibly damaging	0.84
Z1177:Scn2a	UTSW	2	65,548,079 (GRCm39)	missense	probably benign	0.07

Predicted Primers

PCR Primer
(F):5'- ACCTAGAGTCTCTATTCATGTGTGTC -3'
(R):5'- GTCAAAGGAAGCCAACACTG -3'

Sequencing Primer
(F):5'- CATCTTTAGGATATGAACACTTGGGG -3'
(R):5'- ACACTGAGAACTACAGTATAGATTCC -3'

Posted On

2015-04-06