2-166281810-TAA-TAAAAAAAAAA

Variant names:

• chr2-166281810-T-TAAAAAAAA
• rs35888674
• NM_001365536.1:c.1975-10_1975-3dupTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001365536.1(SCN9A):​c.1975-10_1975-3dupTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCN9A NM_001365536.1 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.261
• Publications: 4 publications found

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:54069): (SCN1A and SCN9A antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 2-166281810-T-TAAAAAAAA is Benign according to our data. Variant chr2-166281810-T-TAAAAAAAA is described in ClinVar as Likely_benign. ClinVar VariationId is 471091.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365536.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	NM_001365536.1	MANE Select	c.1975-10_1975-3dupTTTTTTTT		splice_region intron	N/A	NP_001352465.1
	SCN9A	NM_002977.4		c.1942-10_1942-3dupTTTTTTTT		splice_region intron	N/A	NP_002968.2
	SCN1A-AS1	NR_110260.1		n.1029+4566_1029+4573dupAAAAAAAA		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.1975-3_1975-2insTTTTTTTT		splice_region intron	N/A	ENSP00000495601.1
	SCN9A	ENST00000303354.11	TSL:5	c.1975-3_1975-2insTTTTTTTT		splice_region intron	N/A	ENSP00000304748.7
	SCN9A	ENST00000409672.5	TSL:5	c.1942-3_1942-2insTTTTTTTT		splice_region intron	N/A	ENSP00000386306.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1278282 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 634426

African (AFR) AF: 0.00 AC: 0 AN: 28188

American (AMR) AF: 0.00 AC: 0 AN: 34350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21820

East Asian (EAS) AF: 0.00 AC: 0 AN: 33396

South Asian (SAS) AF: 0.00 AC: 0 AN: 71232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 986218

Other (OTH) AF: 0.00 AC: 0 AN: 51986

GnomAD4 genome Cov.: 31

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

Mar 15, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.26

Splicing

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

Other links and lift over

dbSNP: rs35888674; hg19: chr2-167138320;