2-166281810-TA-TAAA

Position:

• chr2-166281810-TA-TAAA

Variant summary

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

The NM_001365536.1(SCN9A):​c.1975-4_1975-3dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,426,264 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00025 (1 hom.)
• Consequence: SCN9A NM_001365536.1 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.261

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 2-166281810-T-TAA is Benign according to our data. Variant chr2-166281810-T-TAA is described in ClinVar as [Likely_benign]. Clinvar id is 696802.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.1975-4_1975-3dupTT		splice_region_variant, intron_variant		ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.1975-4_1975-3dupTT		splice_region_variant, intron_variant			NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.1975-4_1975-3dupTT		splice_region_variant, intron_variant		5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.1942-4_1942-3dupTT		splice_region_variant, intron_variant		5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.1942-4_1942-3dupTT		splice_region_variant, intron_variant				ENSP00000495983.1
SCN9A	ENST00000454569.6	c.1942-4_1942-3dupTT		splice_region_variant, intron_variant		1		ENSP00000413212.2

Frequencies

GnomAD3 genomes AF: 0.0000402 AC: 6 AN: 149284 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000745

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000254 AC: 324 AN: 1276980 Hom.: 1 Cov.: 29 AF XY: 0.000232 AC XY: 147 AN XY: 633768

Gnomad4 AFR exome AF: 0.000107

Gnomad4 AMR exome AF: 0.000175

Gnomad4 ASJ exome AF: 0.000413

Gnomad4 EAS exome AF: 0.0000599

Gnomad4 SAS exome AF: 0.000323

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.000262

Gnomad4 OTH exome AF: 0.000212

GnomAD4 genome AF: 0.0000402 AC: 6 AN: 149284 Hom.: 0 Cov.: 31 AF XY: 0.0000412 AC XY: 3 AN XY: 72792

Gnomad4 AFR AF: 0.0000246

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000745

Gnomad4 OTH AF: 0.00

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

Dec 31, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35888674; hg19: chr2-167138320;