ENST00000359872.6:c.556-372391C>T

Variant names:

• chr17-33484458-G-A
• rs7214958
• ENST00000359872.6:c.556-372391C>T

Variant summary

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

The ENST00000359872.6(ASIC2):​c.556-372391C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,900 control chromosomes in the GnomAD database, including 11,056 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 0.38 (11056 hom., cov: 33)
• Consequence: ASIC2 ENST00000359872.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_001094.5	c.556-372391C>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.556-372391C>T		intron_variant	Intron 1 of 9	1		ENSP00000352934.6

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57571 AN: 151780 Hom.: 11051 Cov.: 33

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.379 AC: 57611 AN: 151900 Hom.: 11056 Cov.: 33 AF XY: 0.376 AC XY: 27911 AN XY: 74232

African (AFR) AF: 0.430 AC: 17808 AN: 41434

American (AMR) AF: 0.330 AC: 5037 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1210 AN: 3472

East Asian (EAS) AF: 0.322 AC: 1658 AN: 5154

South Asian (SAS) AF: 0.286 AC: 1372 AN: 4798

European-Finnish (FIN) AF: 0.399 AC: 4192 AN: 10512

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25272 AN: 67946

Other (OTH) AF: 0.364 AC: 769 AN: 2112

Alfa AF: 0.369 Hom.: 38058

Bravo AF: 0.375

Asia WGS AF: 0.268 AC: 935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.0
DANN	Benign	0.63
PhyloP100		1.3
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: rs7214958; hg19: chr17-31811476;