rs6505380

Variant names:

• chr17-33807275-G-A
• rs6505380
• ENST00000359872.6:c.555+348703C>T

Variant summary

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

The ENST00000359872.6(ASIC2):​c.555+348703C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,092 control chromosomes in the GnomAD database, including 32,055 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 0.64 (32055 hom., cov: 32)
• Consequence: ASIC2 ENST00000359872.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663
• Publications: 8 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]

ENSG00000283417 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_001094.5	c.555+348703C>T		intron_variant	Intron 1 of 9		NP_001085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000359872.6	c.555+348703C>T		intron_variant	Intron 1 of 9	1		ENSP00000352934.6
ENSG00000283417	ENST00000637454.1	n.9+9478C>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97196 AN: 151974 Hom.: 32038 Cov.: 32

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.639 AC: 97251 AN: 152092 Hom.: 32055 Cov.: 32 AF XY: 0.631 AC XY: 46932 AN XY: 74352

African (AFR) AF: 0.605 AC: 25078 AN: 41464

American (AMR) AF: 0.585 AC: 8942 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2184 AN: 3464

East Asian (EAS) AF: 0.173 AC: 898 AN: 5178

South Asian (SAS) AF: 0.433 AC: 2088 AN: 4822

European-Finnish (FIN) AF: 0.697 AC: 7374 AN: 10580

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48509 AN: 67976

Other (OTH) AF: 0.615 AC: 1299 AN: 2112

Alfa AF: 0.680 Hom.: 69202

Bravo AF: 0.633

Asia WGS AF: 0.318 AC: 1111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.3
DANN	Benign	0.81
PhyloP100		0.66
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: rs6505380; hg19: chr17-32134294;