17-33462084-T-C

Variant names:

• chr17-33462084-T-C
• rs952540
• ENST00000359872.6:c.556-350017A>G

Variant summary

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

The NM_001094.5(ASIC2):​c.556-350017A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,074 control chromosomes in the GnomAD database, including 3,266 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 0.20 (3266 hom., cov: 32)
• Consequence: ASIC2 NM_001094.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 2 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=-0.59).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001094.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	NM_001094.5		c.556-350017A>G		intron	N/A	NP_001085.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	ENST00000359872.6	TSL:1	c.556-350017A>G		intron	N/A	ENSP00000352934.6	Q16515-1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30461 AN: 151956 Hom.: 3265 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.200 AC: 30466 AN: 152074 Hom.: 3266 Cov.: 32 AF XY: 0.200 AC XY: 14870 AN XY: 74342

African (AFR) AF: 0.119 AC: 4952 AN: 41494

American (AMR) AF: 0.208 AC: 3180 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 939 AN: 3472

East Asian (EAS) AF: 0.222 AC: 1148 AN: 5166

South Asian (SAS) AF: 0.165 AC: 794 AN: 4810

European-Finnish (FIN) AF: 0.256 AC: 2710 AN: 10570

Middle Eastern (MID) AF: 0.245 AC: 71 AN: 290

European-Non Finnish (NFE) AF: 0.237 AC: 16115 AN: 67960

Other (OTH) AF: 0.221 AC: 466 AN: 2112

Alfa AF: 0.230 Hom.: 7590

Bravo AF: 0.195

Asia WGS AF: 0.176 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.73
PhyloP100		-0.23
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: rs952540; hg19: chr17-31789102;