rs9901756

chr17-34137135-A-C

Variant summary

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

The ENST00000359872.6(ASIC2):c.555+18843T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,242 control chromosomes in the GnomAD database, including 1,368 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 0.13 (1368 hom., cov: 33)
• Consequence: ASIC2 ENST00000359872.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASIC2	NM_001094.5	c.555+18843T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASIC2	ENST00000359872.6	c.555+18843T>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19080 AN: 152124 Hom.: 1364 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0904

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.126 AC: 19113 AN: 152242 Hom.: 1368 Cov.: 33 AF XY: 0.121 AC XY: 9032 AN XY: 74448

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.0954

Gnomad4 ASJ AF: 0.0588

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0905

Gnomad4 FIN AF: 0.0815

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.108

Alfa AF: 0.108 Hom.: 2096

Bravo AF: 0.129

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.029
Dann	Benign	0.42

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: rs9901756; hg19: chr17-32464154;