ENST00000359872.6:c.555+18843T>G

Variant names:

• chr17-34137135-A-C
• rs9901756
• ENST00000359872.6:c.555+18843T>G

Variant summary

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

The ENST00000359872.6(ASIC2):​c.555+18843T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,242 control chromosomes in the GnomAD database, including 1,368 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 0.13 (1368 hom., cov: 33)
• Consequence: ASIC2 ENST00000359872.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 11 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]

ENSG00000265356 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359872.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	NM_001094.5		c.555+18843T>G		intron	N/A	NP_001085.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	ENST00000359872.6	TSL:1	c.555+18843T>G		intron	N/A	ENSP00000352934.6
	ENSG00000265356	ENST00000636421.1	TSL:5	n.241+18625T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19080 AN: 152124 Hom.: 1364 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0904

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.126 AC: 19113 AN: 152242 Hom.: 1368 Cov.: 33 AF XY: 0.121 AC XY: 9032 AN XY: 74448

African (AFR) AF: 0.195 AC: 8089 AN: 41508

American (AMR) AF: 0.0954 AC: 1459 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0588 AC: 204 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5190

South Asian (SAS) AF: 0.0905 AC: 437 AN: 4830

European-Finnish (FIN) AF: 0.0815 AC: 864 AN: 10606

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7708 AN: 68026

Other (OTH) AF: 0.108 AC: 228 AN: 2110

Alfa AF: 0.114 Hom.: 3776

Bravo AF: 0.129

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.029
DANN	Benign	0.42
PhyloP100		-1.7
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: rs9901756; hg19: chr17-32464154;