17-33016157-C-T

Position:

• chr17-33016157-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183377.2(ASIC2):​c.1522-118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 891,490 control chromosomes in the GnomAD database, including 10,049 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1421 hom., cov: 32)
  • Exomes 𝑓: 0.14 (8628 hom.)
• Consequence: ASIC2 NM_183377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.41

Genes affected

ASIC2 (HGNC:99): (acid sensing ion channel subunit 2) This gene encodes a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. The members of this family are amiloride-sensitive sodium channels that contain intracellular N and C termini, 2 hydrophobic transmembrane regions, and a large extracellular loop, which has many cysteine residues with conserved spacing. The member encoded by this gene may play a role in neurotransmission. In addition, a heteromeric association between this member and acid-sensing (proton-gated) ion channel 3 has been observed to co-assemble into proton-gated channels sensitive to gadolinium. Alternative splicing has been observed at this locus and two variants, encoding distinct isoforms, have been identified. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASIC2	NM_183377.2	c.1522-118G>A		intron_variant		ENST00000225823.7
ASIC2	NM_001094.5	c.1369-118G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASIC2	ENST00000225823.7	c.1522-118G>A		intron_variant		1	NM_183377.2
ASIC2	ENST00000359872.6	c.1369-118G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19609 AN: 152126 Hom.: 1420 Cov.: 32

Gnomad AFR AF: 0.0941

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0760

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.142 AC: 104835 AN: 739246 Hom.: 8628 AF XY: 0.140 AC XY: 53765 AN XY: 383376

Gnomad4 AFR exome AF: 0.0975

Gnomad4 AMR exome AF: 0.0920

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.000531

Gnomad4 SAS exome AF: 0.0862

Gnomad4 FIN exome AF: 0.0928

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.129 AC: 19618 AN: 152244 Hom.: 1421 Cov.: 32 AF XY: 0.121 AC XY: 9037 AN XY: 74436

Gnomad4 AFR AF: 0.0941

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0766

Gnomad4 FIN AF: 0.0884

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.133

Alfa AF: 0.117 Hom.: 439

Bravo AF: 0.129

Asia WGS AF: 0.0460 AC: 162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.024
DANN	Benign	0.24

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

LitVar

Other links and lift over

dbSNP: rs3025251; hg19: chr17-31343175; COSMIC: COSV56761177;