rs1394384

Variant names:

• chr17-33462025-T-C
• rs1394384
• ENST00000359872.6:c.556-349958A>G

Variant summary

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

The ENST00000359872.6(ASIC2):​c.556-349958A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,196 control chromosomes in the GnomAD database, including 50,496 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 0.81 (50496 hom., cov: 32)
• Consequence: ASIC2 ENST00000359872.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_001094.5	c.556-349958A>G		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.556-349958A>G		intron_variant	Intron 1 of 9	1		ENSP00000352934.6

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123281 AN: 152076 Hom.: 50432 Cov.: 32

Gnomad AFR AF: 0.919

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.811 AC: 123408 AN: 152196 Hom.: 50496 Cov.: 32 AF XY: 0.807 AC XY: 60059 AN XY: 74396

African (AFR) AF: 0.919 AC: 38168 AN: 41542

American (AMR) AF: 0.692 AC: 10578 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2549 AN: 3472

East Asian (EAS) AF: 0.648 AC: 3343 AN: 5162

South Asian (SAS) AF: 0.839 AC: 4034 AN: 4810

European-Finnish (FIN) AF: 0.786 AC: 8322 AN: 10594

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53851 AN: 68016

Other (OTH) AF: 0.772 AC: 1629 AN: 2110

Alfa AF: 0.804 Hom.: 10234

Bravo AF: 0.804

Asia WGS AF: 0.777 AC: 2702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.51
PhyloP100		-0.15
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: rs1394384; hg19: chr17-31789043;