rs2074215

chr17-33017531-T-C

Variant summary

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

The NM_183377.2(ASIC2):c.1521+74A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 1,299,808 control chromosomes in the GnomAD database, including 201,882 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 0.60 (28862 hom., cov: 32)
  • Exomes 𝑓: 0.54 (173020 hom.)
• Consequence: ASIC2 NM_183377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432

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 (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASIC2	NM_183377.2	c.1521+74A>G		intron_variant		ENST00000225823.7
ASIC2	NM_001094.5	c.1368+74A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASIC2	ENST00000225823.7	c.1521+74A>G		intron_variant		1	NM_183377.2
ASIC2	ENST00000359872.6	c.1368+74A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91562 AN: 152060 Hom.: 28823 Cov.: 32

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.592

GnomAD4 exome AF: 0.544 AC: 624819 AN: 1147630 Hom.: 173020 AF XY: 0.545 AC XY: 316515 AN XY: 580498

Gnomad4 AFR exome AF: 0.806

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.621

Gnomad4 EAS exome AF: 0.557

Gnomad4 SAS exome AF: 0.549

Gnomad4 FIN exome AF: 0.511

Gnomad4 NFE exome AF: 0.543

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.602 AC: 91649 AN: 152178 Hom.: 28862 Cov.: 32 AF XY: 0.597 AC XY: 44405 AN XY: 74408

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.594

Alfa AF: 0.562 Hom.: 4519

Bravo AF: 0.604

Asia WGS AF: 0.573 AC: 1989 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	2.2
Dann	Benign	0.34

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: rs2074215; hg19: chr17-31344549; COSMIC: COSV56767089;