2-166204084-A-T

Position:

• chr2-166204084-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001365536.1(SCN9A):​c.4645T>A​(p.Trp1549Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Benignin Lovd.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCN9A NM_001365536.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.17

Genes affected

SCN9A (HGNC:10597): (sodium voltage-gated channel alpha subunit 9) This gene encodes a voltage-gated sodium channel which plays a significant role in nociception signaling. Mutations in this gene have been associated with primary erythermalgia, channelopathy-associated insensitivity to pain, and paroxysmal extreme pain disorder. [provided by RefSeq, Aug 2009]

SCN1A-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 2-166204084-A-T is Benign according to our data. Variant chr2-166204084-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1152102.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.4645T>A	p.Trp1549Arg	missense_variant	26/27	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.4645T>A	p.Trp1549Arg	missense_variant	26/27		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.4645T>A	p.Trp1549Arg	missense_variant	26/27	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.4612T>A	p.Trp1538Arg	missense_variant	26/27	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.4612T>A	p.Trp1538Arg	missense_variant	26/27			ENSP00000495983.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 09, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Benign	19
DANN	Benign	0.83
DEOGEN2	Uncertain	0.72	.;D;.;.;D;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.61	T;.;T;T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.63	D;D;D;D;D;D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Benign	0.81	.;L;.;.;L;L
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.7	D;.;.;.;.;D
REVEL	Pathogenic	0.67
Sift	Benign	0.92	T;.;.;.;.;T
Sift4G	Benign	0.36	T;T;.;.;.;T
Vest4		0.82
MutPred		0.65		Loss of catalytic residue at L1536 (P = 0.0064);.;Loss of catalytic residue at L1536 (P = 0.0064);.;.;.;
MVP		0.72
MPC		0.24
ClinPred		0.78	D
GERP RS		4.5
Varity_R		0.60
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-167060594;