rs63953

Positions:

• chr17-33330590-G-A
• chr17-33330590-G-C
• chr17-33330590-G-T

Variant summary

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

The ENST00000359872.6(ASIC2):​c.556-218523C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 151,964 control chromosomes in the GnomAD database, including 35,672 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 0.68 (35672 hom., cov: 31)
• Consequence: ASIC2 ENST00000359872.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASIC2	NM_001094.5	c.556-218523C>T		intron_variant			NP_001085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000359872.6	c.556-218523C>T		intron_variant		1		ENSP00000352934	P1

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103182 AN: 151846 Hom.: 35638 Cov.: 31

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.680 AC: 103260 AN: 151964 Hom.: 35672 Cov.: 31 AF XY: 0.686 AC XY: 50949 AN XY: 74284

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.968

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.662

Alfa AF: 0.695 Hom.: 49136

Bravo AF: 0.676

Asia WGS AF: 0.857 AC: 2982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.46

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: rs63953; hg19: chr17-31657608;