17-34095680-G-T

Variant names:

• chr17-34095680-G-T
• rs116908816
• ENST00000359872.6:c.555+60298C>A

Variant summary

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

The NM_001094.5(ASIC2):​c.555+60298C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 124,146 control chromosomes in the GnomAD database, including 1,790 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 0.16 (1790 hom., cov: 23)
• Consequence: ASIC2 NM_001094.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04
• 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]

ENSG00000263485 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 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.555+60298C>A		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.555+60298C>A		intron	N/A	ENSP00000352934.6
	ENSG00000263485	ENST00000580658.2	TSL:3	n.110-6430C>A		intron	N/A
	ENSG00000265356	ENST00000636421.1	TSL:5	n.242-43944C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.162 AC: 20129 AN: 124154 Hom.: 1785 Cov.: 23

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0791

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.162 AC: 20132 AN: 124146 Hom.: 1790 Cov.: 23 AF XY: 0.160 AC XY: 9532 AN XY: 59592

African (AFR) AF: 0.237 AC: 8445 AN: 35596

American (AMR) AF: 0.216 AC: 2693 AN: 12478

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 323 AN: 2904

East Asian (EAS) AF: 0.0792 AC: 338 AN: 4270

South Asian (SAS) AF: 0.205 AC: 814 AN: 3976

European-Finnish (FIN) AF: 0.0541 AC: 308 AN: 5696

Middle Eastern (MID) AF: 0.103 AC: 24 AN: 232

European-Non Finnish (NFE) AF: 0.121 AC: 6837 AN: 56506

Other (OTH) AF: 0.140 AC: 233 AN: 1666

Alfa AF: 0.0328 Hom.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.37
DANN	Benign	0.12
PhyloP100		-3.0
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: rs116908816; hg19: chr17-32422699; COSMIC: COSV63330297;