Mutagenetix > Incidental Mutation

Incidental Mutation 'R9452:Scn2a'

714309

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

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R9452 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

65451115-65597791 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 65595163 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Asparagine at position 2004 (S2004N)

Ref Sequence

ENSEMBL: ENSMUSP00000028377 (fasta)

Gene Model

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

AlphaFold

B1AWN6

Predicted Effect

probably benign
Transcript: ENSMUST00000028377
AA Change: S2004N

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000028377
Gene: ENSMUSG00000075318
AA Change: S2004N

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: S2004N

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000097645
Gene: ENSMUSG00000075318
AA Change: S2004N

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: S2004N

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000143882
Gene: ENSMUSG00000075318
AA Change: S2004N

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.7%

Validation Efficiency

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: 69 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb8	A	G	5: 24,612,382 (GRCm39)	Y564C	probably null	Het
Ablim2	A	T	5: 36,015,198 (GRCm39)	D470V	probably benign	Het
Actr10	T	C	12: 71,006,818 (GRCm39)		probably null	Het
Adam4	T	A	12: 81,467,071 (GRCm39)	I517L	probably benign	Het
Ank1	C	A	8: 23,622,429 (GRCm39)	D1659E	probably benign	Het
Arnt2	A	G	7: 83,933,334 (GRCm39)	V308A	probably benign	Het
Avl9	T	C	6: 56,706,726 (GRCm39)	V184A	probably damaging	Het
Bag1	A	T	4: 40,947,733 (GRCm39)	I157N	probably benign	Het
Bicc1	A	T	10: 70,792,981 (GRCm39)	D224E	probably damaging	Het
C2	T	G	17: 35,095,319 (GRCm39)	I209L	probably benign	Het
Cacna1e	A	T	1: 154,289,720 (GRCm39)		probably null	Het
Capn1	T	C	19: 6,057,287 (GRCm39)	Y387C	probably damaging	Het
Cebpa	A	G	7: 34,819,033 (GRCm39)	I64V	possibly damaging	Het
Celf4	T	G	18: 25,624,219 (GRCm39)	M436L	probably benign	Het
Cfb	C	A	17: 35,078,084 (GRCm39)	V436L	probably benign	Het
Ciart	C	T	3: 95,788,527 (GRCm39)	C104Y	probably benign	Het
Cmya5	A	G	13: 93,232,394 (GRCm39)	L898P	probably benign	Het
Cyp2c68	A	T	19: 39,687,833 (GRCm39)	M388K	possibly damaging	Het
Cypt12	T	C	3: 18,002,843 (GRCm39)	V72A	probably benign	Het
Dlec1	A	G	9: 118,941,541 (GRCm39)	D309G	probably benign	Het
Dnah1	A	G	14: 31,018,448 (GRCm39)	V1394A	probably benign	Het
Dpp3	A	C	19: 4,973,750 (GRCm39)	S108A	probably benign	Het
Eif5b	C	T	1: 38,084,861 (GRCm39)	P903S	probably damaging	Het
Erc2	A	G	14: 27,733,690 (GRCm39)	D580G	probably damaging	Het
Fam98c	A	G	7: 28,852,901 (GRCm39)	V44A	probably benign	Het
Fer	A	G	17: 64,231,067 (GRCm39)	K273E	probably benign	Het
Gzme	T	A	14: 56,355,854 (GRCm39)	I153F	probably benign	Het
Ice1	A	T	13: 70,744,462 (GRCm39)	N2040K	probably damaging	Het
Ifi214	G	T	1: 173,356,894 (GRCm39)	Q70K	possibly damaging	Het
Itpripl1	C	A	2: 126,983,334 (GRCm39)	E263*	probably null	Het
Kat8	A	G	7: 127,524,421 (GRCm39)	K433R	probably benign	Het
Klra5	C	A	6: 129,883,686 (GRCm39)	W147L	possibly damaging	Het
Lefty1	A	T	1: 180,762,849 (GRCm39)	T59S	probably benign	Het
Lig3	C	T	11: 82,681,448 (GRCm39)	T481M	probably damaging	Het
Lrfn1	A	T	7: 28,159,157 (GRCm39)	I359F	probably damaging	Het
Lrp1b	A	T	2: 41,850,726 (GRCm39)	C90*	probably null	Het
Micall2	T	G	5: 139,703,311 (GRCm39)		probably null	Het
Mtmr3	G	T	11: 4,441,037 (GRCm39)	L539I	probably damaging	Het
Obscn	C	A	11: 58,924,962 (GRCm39)		probably null	Het
Olfml3	T	C	3: 103,643,575 (GRCm39)	T269A	probably benign	Het
Oprl1	C	T	2: 181,360,454 (GRCm39)	A170V	possibly damaging	Het
Or4c112	C	T	2: 88,854,234 (GRCm39)	G38R		Het
Pdgfrb	G	A	18: 61,198,798 (GRCm39)	V319M	possibly damaging	Het
Pirb	G	A	7: 3,720,617 (GRCm39)	R294C	possibly damaging	Het
Piwil1	T	C	5: 128,824,957 (GRCm39)	S552P	probably benign	Het
Pkd2	T	C	5: 104,614,841 (GRCm39)	F228L	probably damaging	Het
Pkhd1	T	A	1: 20,682,953 (GRCm39)	D83V	possibly damaging	Het
Plcl1	A	G	1: 55,734,992 (GRCm39)	D111G	probably damaging	Het
Plpp2	A	G	10: 79,363,702 (GRCm39)	S162P	probably damaging	Het
Prex2	T	A	1: 11,256,151 (GRCm39)	I1174K	probably benign	Het
Prkdc	T	A	16: 15,485,465 (GRCm39)	Y431N	possibly damaging	Het
Pter	A	G	2: 12,985,111 (GRCm39)	D147G	probably benign	Het
Rbsn	T	C	6: 92,178,745 (GRCm39)	D134G	possibly damaging	Het
Rnf220	T	C	4: 117,153,339 (GRCm39)	D299G	probably benign	Het
Rsf1	CGGCGGCGG	CGGCGGCGGGGGCGGCGG	7: 97,229,133 (GRCm39)		probably benign	Het
Slc7a4	T	A	16: 17,391,271 (GRCm39)	N593I	probably damaging	Het
Spata31e3	T	C	13: 50,400,808 (GRCm39)	H506R	possibly damaging	Het
Speg	T	C	1: 75,399,152 (GRCm39)	S2200P	probably benign	Het
Thoc2l	T	A	5: 104,669,610 (GRCm39)	N1377K	probably benign	Het
Tle1	A	T	4: 72,040,596 (GRCm39)	H654Q	probably benign	Het
Ttll6	G	A	11: 96,026,588 (GRCm39)	R124H	probably damaging	Het
Vmn2r111	A	G	17: 22,778,132 (GRCm39)	C516R	probably damaging	Het
Vmn2r89	T	C	14: 51,693,288 (GRCm39)	S213P	probably damaging	Het
Vmn2r-ps158	A	T	7: 42,697,257 (GRCm39)	L771F	possibly damaging	Het
Washc4	A	G	10: 83,396,387 (GRCm39)	N399S	probably benign	Het
Wdr37	G	A	13: 8,897,663 (GRCm39)	H198Y		Het
Zfp407	A	G	18: 84,580,579 (GRCm39)	L178P	probably benign	Het
Zfp882	C	T	8: 72,668,831 (GRCm39)	H553Y	probably damaging	Het
Zfp956	T	C	6: 47,940,370 (GRCm39)	V243A	probably benign	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
R3850:Scn2a	UTSW	2	65,512,375 (GRCm39)	missense	probably benign	0.14
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
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'- GCGAGCTTACAGACGCTATC -3'
(R):5'- TGTCTGGTTATAGGCACTGACC -3'

Sequencing Primer
(F):5'- GCTTACAGACGCTATCTTCTGAAAC -3'
(R):5'- CTGGTTATAGGCACTGACCTTAAG -3'

Posted On

2022-06-15