chr17-33413163-G-A

Variant names:

• chr17-33413163-G-A
• rs12941510
• ENST00000359872.6:c.556-301096C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000359872.6(ASIC2):​c.556-301096C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,034 control chromosomes in the GnomAD database, including 6,738 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 0.27 (6738 hom., cov: 32)
• Consequence: ASIC2 ENST00000359872.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.936
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_001094.5	c.556-301096C>T		intron_variant	Intron 1 of 9		NP_001085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000359872.6	c.556-301096C>T		intron_variant	Intron 1 of 9	1		ENSP00000352934.6

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40389 AN: 151916 Hom.: 6740 Cov.: 32

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.266

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.266 AC: 40390 AN: 152034 Hom.: 6738 Cov.: 32 AF XY: 0.268 AC XY: 19885 AN XY: 74280

African (AFR) AF: 0.0664 AC: 2755 AN: 41508

American (AMR) AF: 0.288 AC: 4396 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 880 AN: 3470

East Asian (EAS) AF: 0.183 AC: 944 AN: 5156

South Asian (SAS) AF: 0.312 AC: 1500 AN: 4804

European-Finnish (FIN) AF: 0.416 AC: 4390 AN: 10552

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.359 AC: 24428 AN: 67952

Other (OTH) AF: 0.264 AC: 556 AN: 2108

Alfa AF: 0.322 Hom.: 14658

Bravo AF: 0.245

Asia WGS AF: 0.194 AC: 677 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
DANN	Benign	0.85
PhyloP100		0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12941510; hg19: chr17-31740181; COSMIC: COSV63330867;