chr17-33017531-T-C

Variant names:

• chr17-33017531-T-C
• rs2074215
• NM_183377.2:c.1521+74A>G

Variant summary

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

The NM_183377.2(ASIC2):​c.1521+74A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 1,299,808 control chromosomes in the GnomAD database, including 201,882 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 0.60 (28862 hom., cov: 32)
  • Exomes 𝑓: 0.54 (173020 hom.)
• Consequence: ASIC2 NM_183377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183377.2. 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_183377.2	MANE Select	c.1521+74A>G		intron	N/A	NP_899233.1
	ASIC2	NM_001094.5		c.1368+74A>G		intron	N/A	NP_001085.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	ENST00000225823.7	TSL:1 MANE Select	c.1521+74A>G		intron	N/A	ENSP00000225823.2
	ASIC2	ENST00000359872.6	TSL:1	c.1368+74A>G		intron	N/A	ENSP00000352934.6

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91562 AN: 152060 Hom.: 28823 Cov.: 32

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.592

GnomAD4 exome AF: 0.544 AC: 624819 AN: 1147630 Hom.: 173020 AF XY: 0.545 AC XY: 316515 AN XY: 580498

African (AFR) AF: 0.806 AC: 21329 AN: 26474

American (AMR) AF: 0.346 AC: 13699 AN: 39614

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 13805 AN: 22234

East Asian (EAS) AF: 0.557 AC: 20793 AN: 37326

South Asian (SAS) AF: 0.549 AC: 39773 AN: 72500

European-Finnish (FIN) AF: 0.511 AC: 25506 AN: 49938

Middle Eastern (MID) AF: 0.638 AC: 3188 AN: 4994

European-Non Finnish (NFE) AF: 0.543 AC: 458559 AN: 844794

Other (OTH) AF: 0.566 AC: 28167 AN: 49756

GnomAD4 genome AF: 0.602 AC: 91649 AN: 152178 Hom.: 28862 Cov.: 32 AF XY: 0.597 AC XY: 44405 AN XY: 74408

African (AFR) AF: 0.794 AC: 32974 AN: 41546

American (AMR) AF: 0.448 AC: 6847 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2125 AN: 3464

East Asian (EAS) AF: 0.526 AC: 2719 AN: 5166

South Asian (SAS) AF: 0.557 AC: 2683 AN: 4820

European-Finnish (FIN) AF: 0.513 AC: 5432 AN: 10584

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36876 AN: 67980

Other (OTH) AF: 0.594 AC: 1256 AN: 2114

Alfa AF: 0.568 Hom.: 4761

Bravo AF: 0.604

Asia WGS AF: 0.573 AC: 1989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.34
PhyloP100		-0.43
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: rs2074215; hg19: chr17-31344549; COSMIC: COSV56767089;