rs317397

Positions:

• chr17-33849627-T-C
• chr17-33849627-T-G

Variant summary

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

The NM_001094.5(ASIC2):​c.555+306351A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,902 control chromosomes in the GnomAD database, including 8,571 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 0.32 (8571 hom., cov: 32)
• Consequence: ASIC2 NM_001094.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.13

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]

ENSG00000279668 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASIC2	NM_001094.5	c.555+306351A>G		intron_variant			NP_001085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000359872.6	c.555+306351A>G		intron_variant		1		ENSP00000352934.6
ENSG00000279668	ENST00000636687.1	n.131-21146A>G		intron_variant		5
ENSG00000279668	ENST00000637947.1	n.87-21146A>G		intron_variant		5
ENSG00000279668	ENST00000659958.1	n.131-21146A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49250 AN: 151786 Hom.: 8552 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.325 AC: 49315 AN: 151902 Hom.: 8571 Cov.: 32 AF XY: 0.334 AC XY: 24798 AN XY: 74228

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.274

Alfa AF: 0.257 Hom.: 11001

Bravo AF: 0.328

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.44
DANN	Benign	0.30

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: rs317397; hg19: chr17-32176646;