17-33013664-C-T

Position:

• chr17-33013664-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.*301G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 393,850 control chromosomes in the GnomAD database, including 36,273 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 0.45 (18069 hom., cov: 32)
  • Exomes 𝑓: 0.37 (18204 hom.)
• Consequence: ASIC2 NM_183377.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASIC2	NM_183377.2	c.*301G>A		3_prime_UTR_variant	10/10	ENST00000225823.7	NP_899233.1
ASIC2	NM_001094.5	c.*301G>A		3_prime_UTR_variant	10/10		NP_001085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000225823	c.*301G>A		3_prime_UTR_variant	10/10	1	NM_183377.2	ENSP00000225823.2
ASIC2	ENST00000359872.6	c.*301G>A		3_prime_UTR_variant	10/10	1		ENSP00000352934.6

Frequencies

GnomAD3 genomes AF: 0.454 AC: 69058 AN: 151958 Hom.: 18026 Cov.: 32

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.459

GnomAD4 exome AF: 0.373 AC: 90105 AN: 241774 Hom.: 18204 Cov.: 0 AF XY: 0.373 AC XY: 46604 AN XY: 124858

Gnomad4 AFR exome AF: 0.725

Gnomad4 AMR exome AF: 0.271

Gnomad4 ASJ exome AF: 0.412

Gnomad4 EAS exome AF: 0.463

Gnomad4 SAS exome AF: 0.379

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.356

Gnomad4 OTH exome AF: 0.396

GnomAD4 genome AF: 0.455 AC: 69158 AN: 152076 Hom.: 18069 Cov.: 32 AF XY: 0.447 AC XY: 33207 AN XY: 74346

Gnomad4 AFR AF: 0.723

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.463

Alfa AF: 0.385 Hom.: 16416

Bravo AF: 0.472

Asia WGS AF: 0.454 AC: 1578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.81

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: rs28933; hg19: chr17-31340682; COSMIC: COSV56772421;