ENST00000359872.6:c.315T>C

Variant names:

• chr17-34156218-A-G
• rs2228990
• ENST00000359872.6:c.315T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000359872.6(ASIC2):​c.315T>C​(p.Asn105Asn) 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
• Publications: 13 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]

ENSG00000263571 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ASIC2	NM_001094.5	c.315T>C	p.Asn105Asn	synonymous_variant	Exon 1 of 10		NP_001085.2
LOC105371735	NR_188344.1	n.620A>G		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000359872.6	c.315T>C	p.Asn105Asn	synonymous_variant	Exon 1 of 10	1		ENSP00000352934.6
ENSG00000263571	ENST00000583224.3	n.653A>G		non_coding_transcript_exon_variant	Exon 1 of 4	5
ENSG00000263571	ENST00000667899.1	n.605A>G		non_coding_transcript_exon_variant	Exon 1 of 3
ENSG00000265356	ENST00000636421.1	n.-218T>C		upstream_gene_variant		5

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

GnomAD2 exomes AF: 0.246 AC: 61499 AN: 249508 AF XY: 0.242

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 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

African (AFR) AF: 0.176 AC: 5902 AN: 33480

American (AMR) AF: 0.401 AC: 17913 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 4398 AN: 26136

East Asian (EAS) AF: 0.340 AC: 13499 AN: 39700

South Asian (SAS) AF: 0.288 AC: 24854 AN: 86258

European-Finnish (FIN) AF: 0.229 AC: 12252 AN: 53412

Middle Eastern (MID) AF: 0.215 AC: 1240 AN: 5766

European-Non Finnish (NFE) AF: 0.193 AC: 214439 AN: 1111976

Other (OTH) AF: 0.215 AC: 13002 AN: 60394

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

African (AFR) AF: 0.179 AC: 7447 AN: 41498

American (AMR) AF: 0.333 AC: 5088 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3470

East Asian (EAS) AF: 0.353 AC: 1811 AN: 5128

South Asian (SAS) AF: 0.302 AC: 1459 AN: 4826

European-Finnish (FIN) AF: 0.235 AC: 2487 AN: 10580

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13231 AN: 67982

Other (OTH) AF: 0.210 AC: 444 AN: 2110

Alfa AF: 0.204 Hom.: 3727

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
PhyloP100		-0.28
Mutation Taster		=89/11	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: rs2228990; hg19: chr17-32483237; COSMIC: COSV63310034; COSMIC: COSV63310034;