17-33095521-G-C

Variant names:

• chr17-33095521-G-C
• rs4289044
• NM_183377.2:c.860-6531C>G

Variant summary

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

The NM_183377.2(ASIC2):​c.860-6531C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 152,210 control chromosomes in the GnomAD database, including 47,059 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 0.79 (47059 hom., cov: 33)
• Consequence: ASIC2 NM_183377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 3 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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_183377.2	c.860-6531C>G		intron_variant	Intron 2 of 9	ENST00000225823.7	NP_899233.1
ASIC2	NM_001094.5	c.707-6531C>G		intron_variant	Intron 2 of 9		NP_001085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000225823.7	c.860-6531C>G		intron_variant	Intron 2 of 9	1	NM_183377.2	ENSP00000225823.2
ASIC2	ENST00000359872.6	c.707-6531C>G		intron_variant	Intron 2 of 9	1		ENSP00000352934.6
ASIC2	ENST00000448983.1	n.265-6531C>G		intron_variant	Intron 3 of 6	3

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119511 AN: 152092 Hom.: 47027 Cov.: 33

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.789

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

GnomAD4 genome AF: 0.786 AC: 119601 AN: 152210 Hom.: 47059 Cov.: 33 AF XY: 0.786 AC XY: 58501 AN XY: 74422

African (AFR) AF: 0.736 AC: 30560 AN: 41500

American (AMR) AF: 0.816 AC: 12497 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2976 AN: 3470

East Asian (EAS) AF: 0.881 AC: 4565 AN: 5184

South Asian (SAS) AF: 0.858 AC: 4140 AN: 4826

European-Finnish (FIN) AF: 0.761 AC: 8064 AN: 10592

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54129 AN: 68018

Other (OTH) AF: 0.788 AC: 1662 AN: 2108

Alfa AF: 0.730 Hom.: 2125

Bravo AF: 0.788

Asia WGS AF: 0.860 AC: 2991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.6
DANN	Benign	0.47
PhyloP100		-0.040
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: rs4289044; hg19: chr17-31422539;