ENST00000359872.6:c.555+60298C>A

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 ENST00000359872.6(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 ENST00000359872.6 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_001094.5	c.555+60298C>A		intron_variant	Intron 1 of 9		NP_001085.2
LOC107985036	XR_001752835.1	n.673-1647C>A		intron_variant	Intron 6 of 7
LOC107985036	XR_007065717.1	n.1130-1647C>A		intron_variant	Intron 5 of 6
LOC107985036	XR_007065718.1	n.1100-1647C>A		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000359872.6	c.555+60298C>A		intron_variant	Intron 1 of 9	1		ENSP00000352934.6
ENSG00000263485	ENST00000580658.2	n.110-6430C>A		intron_variant	Intron 1 of 4	3
ENSG00000265356	ENST00000636421.1	n.242-43944C>A		intron_variant	Intron 1 of 3	5
ENSG00000263485	ENST00000836207.1	n.263-6430C>A		intron_variant	Intron 1 of 3

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 v4.3

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;