rs439783

chr17-33350142-T-C

Variant summary

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

The ENST00000359872.6(ASIC2):c.556-238075A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,930 control chromosomes in the GnomAD database, including 18,754 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 0.48 (18754 hom., cov: 32)
• Consequence: ASIC2 ENST00000359872.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASIC2	NM_001094.5	c.556-238075A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASIC2	ENST00000359872.6	c.556-238075A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73484 AN: 151812 Hom.: 18719 Cov.: 32

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.484 AC: 73570 AN: 151930 Hom.: 18754 Cov.: 32 AF XY: 0.486 AC XY: 36091 AN XY: 74250

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.434

Alfa AF: 0.412 Hom.: 18436

Bravo AF: 0.491

Asia WGS AF: 0.597 AC: 2077 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	0.10
Dann	Benign	0.65

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: rs439783; hg19: chr17-31677160;