rs2228990

Positions:

• chr17-34156218-A-G
• chr17-34156218-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000359872.6(ASIC2):​c.315T>C​(p.Asn105=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,613,928 control chromosomes in the GnomAD database, including 38,440 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 0.22 (3793 hom., cov: 32)
  • Exomes 𝑓: 0.21 (34647 hom.)
• Consequence: ASIC2 ENST00000359872.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-0.275 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASIC2	NM_001094.5	c.315T>C	p.Asn105=	synonymous_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASIC2	ENST00000359872.6	c.315T>C	p.Asn105=	synonymous_variant	1/10	1		P1
	ENST00000583224.3	n.653A>G		non_coding_transcript_exon_variant	1/4	5
	ENST00000667899.1	n.605A>G		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32739 AN: 151966 Hom.: 3788 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.207

GnomAD3 exomes AF: 0.246 AC: 61499 AN: 249508 Hom.: 8626 AF XY: 0.242 AC XY: 32740 AN XY: 135346

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.415

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.346

Gnomad SAS exome AF: 0.289

Gnomad FIN exome AF: 0.229

Gnomad NFE exome AF: 0.190

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.210 AC: 307499 AN: 1461842 Hom.: 34647 Cov.: 33 AF XY: 0.212 AC XY: 153970 AN XY: 727222

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.401

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.215 AC: 32772 AN: 152086 Hom.: 3793 Cov.: 32 AF XY: 0.222 AC XY: 16502 AN XY: 74362

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.210

Alfa AF: 0.201 Hom.: 2360

Bravo AF: 0.220

Asia WGS AF: 0.318 AC: 1106 AN: 3478

EpiCase AF: 0.198

EpiControl AF: 0.190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.2
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs2228990; hg19: chr17-32483237; COSMIC: COSV63310034; COSMIC: COSV63310034;