17-33622760-C-T

Variant names:

• chr17-33622760-C-T
• rs1560916
• ENST00000359872.6:c.556-510693G>A

Variant summary

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

The NM_001094.5(ASIC2):​c.556-510693G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,048 control chromosomes in the GnomAD database, including 21,377 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 0.52 (21377 hom., cov: 33)
• Consequence: ASIC2 NM_001094.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.428

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]

ENSG00000265125 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_001094.5	c.556-510693G>A		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.556-510693G>A		intron_variant	Intron 1 of 9	1		ENSP00000352934.6
ENSG00000265125	ENST00000579975.1	n.509-694C>T		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79372 AN: 151928 Hom.: 21345 Cov.: 33

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.522 AC: 79442 AN: 152048 Hom.: 21377 Cov.: 33 AF XY: 0.512 AC XY: 38032 AN XY: 74286

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.508

Alfa AF: 0.512 Hom.: 40318

Bravo AF: 0.531

Asia WGS AF: 0.439 AC: 1530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.2
DANN	Benign	0.79

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: rs1560916; hg19: chr17-31949779;