17-33662211-C-T

Variant names:

• chr17-33662211-C-T
• rs280039
• ENST00000359872.6:c.555+493767G>A

Variant summary

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

The ENST00000359872.6(ASIC2):​c.555+493767G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 151,904 control chromosomes in the GnomAD database, including 30,074 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 0.63 (30074 hom., cov: 31)
• Consequence: ASIC2 ENST00000359872.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_001094.5	c.555+493767G>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.555+493767G>A		intron_variant	Intron 1 of 9	1		ENSP00000352934.6

Frequencies

GnomAD3 genomes AF: 0.626 AC: 94968 AN: 151786 Hom.: 30030 Cov.: 31

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.626 AC: 95067 AN: 151904 Hom.: 30074 Cov.: 31 AF XY: 0.625 AC XY: 46364 AN XY: 74212

African (AFR) AF: 0.722 AC: 29911 AN: 41438

American (AMR) AF: 0.645 AC: 9836 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1974 AN: 3470

East Asian (EAS) AF: 0.546 AC: 2817 AN: 5156

South Asian (SAS) AF: 0.697 AC: 3360 AN: 4818

European-Finnish (FIN) AF: 0.551 AC: 5784 AN: 10504

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39406 AN: 67960

Other (OTH) AF: 0.584 AC: 1233 AN: 2110

Alfa AF: 0.590 Hom.: 41926

Bravo AF: 0.634

Asia WGS AF: 0.642 AC: 2232 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	0.48
DANN	Benign	0.44
PhyloP100		-0.30
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: rs280039; hg19: chr17-31989230;