2-166196045-CTTAAAAAAGTT-C

Position:

• chr2-166196045-CTTAAAAAAGTT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001365536.1(SCN9A):​c.*2616_*2626del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,348 control chromosomes in the GnomAD database, including 17,861 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (17859 hom., cov: 0)
  • Exomes 𝑓: 0.50 (2 hom.)
• Consequence: SCN9A NM_001365536.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:7
• Conservation: PhyloP100: 1.70

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-166196045-CTTAAAAAAGTT-C is Benign according to our data. Variant chr2-166196045-CTTAAAAAAGTT-C is described in ClinVar as [Benign]. Clinvar id is 331908.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.*2616_*2626del		3_prime_UTR_variant	27/27	ENST00000642356.2	NP_001352465.1
SCN1A-AS1	NR_110260.1	n.432-3591_432-3581del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.*2616_*2626del		3_prime_UTR_variant	27/27		NM_001365536.1	ENSP00000495601	P1
SCN1A-AS1	ENST00000651574.1	n.1110-3591_1110-3581del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.482 AC: 72888 AN: 151206 Hom.: 17854 Cov.: 0

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.469

GnomAD4 exome AF: 0.500 AC: 11 AN: 22 Hom.: 2 AF XY: 0.500 AC XY: 10 AN XY: 20

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.482 AC: 72916 AN: 151326 Hom.: 17859 Cov.: 0 AF XY: 0.476 AC XY: 35225 AN XY: 73928

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.467

Alfa AF: 0.492 Hom.: 2236

Bravo AF: 0.481

Asia WGS AF: 0.460 AC: 1601 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, single submitter

Submissions by phenotype

Inherited Erythromelalgia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Generalized epilepsy with febrile seizures plus Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Congenital Indifference to Pain Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Small fiber neuropathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Paroxysmal extreme pain disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Febrile seizures, familial Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Severe myoclonic epilepsy in infancy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs145255931; hg19: chr2-167052555;