NM_183377.2:c.1522-118G>A

Variant names:

• chr17-33016157-C-T
• rs3025251
• NM_183377.2:c.1522-118G>A

Variant summary

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

The NM_183377.2(ASIC2):​c.1522-118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 891,490 control chromosomes in the GnomAD database, including 10,049 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 (1421 hom., cov: 32)
  • Exomes 𝑓: 0.14 (8628 hom.)
• Consequence: ASIC2 NM_183377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.41
• Publications: 3 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 (NFE) allele frequency at 95% confidence interval = 0.166 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	NM_183377.2	MANE Select	c.1522-118G>A		intron	N/A	NP_899233.1	Q16515-2
	ASIC2	NM_001094.5		c.1369-118G>A		intron	N/A	NP_001085.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	ENST00000225823.7	TSL:1 MANE Select	c.1522-118G>A		intron	N/A	ENSP00000225823.2	Q16515-2
	ASIC2	ENST00000359872.6	TSL:1	c.1369-118G>A		intron	N/A	ENSP00000352934.6	Q16515-1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19609 AN: 152126 Hom.: 1420 Cov.: 32

Gnomad AFR AF: 0.0941

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0760

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.142 AC: 104835 AN: 739246 Hom.: 8628 AF XY: 0.140 AC XY: 53765 AN XY: 383376

African (AFR) AF: 0.0975 AC: 1864 AN: 19112

American (AMR) AF: 0.0920 AC: 2784 AN: 30264

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 3578 AN: 17654

East Asian (EAS) AF: 0.000531 AC: 18 AN: 33918

South Asian (SAS) AF: 0.0862 AC: 5116 AN: 59374

European-Finnish (FIN) AF: 0.0928 AC: 4050 AN: 43630

Middle Eastern (MID) AF: 0.174 AC: 451 AN: 2588

European-Non Finnish (NFE) AF: 0.164 AC: 81678 AN: 497188

Other (OTH) AF: 0.149 AC: 5296 AN: 35518

GnomAD4 genome AF: 0.129 AC: 19618 AN: 152244 Hom.: 1421 Cov.: 32 AF XY: 0.121 AC XY: 9037 AN XY: 74436

African (AFR) AF: 0.0941 AC: 3909 AN: 41548

American (AMR) AF: 0.110 AC: 1684 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3472

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5176

South Asian (SAS) AF: 0.0766 AC: 370 AN: 4828

European-Finnish (FIN) AF: 0.0884 AC: 938 AN: 10606

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11473 AN: 68006

Other (OTH) AF: 0.133 AC: 279 AN: 2104

Alfa AF: 0.123 Hom.: 579

Bravo AF: 0.129

Asia WGS AF: 0.0460 AC: 162 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	0.024
DANN	Benign	0.24
PhyloP100		-3.4
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: rs3025251; hg19: chr17-31343175; COSMIC: COSV56761177;