chr17-33013664-C-T

Variant names:

• chr17-33013664-C-T
• rs28933
• NM_183377.2:c.*301G>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.*301G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 393,850 control chromosomes in the GnomAD database, including 36,273 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 0.45 (18069 hom., cov: 32)
  • Exomes 𝑓: 0.37 (18204 hom.)
• Consequence: ASIC2 NM_183377.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 10 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=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 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.*301G>A		3_prime_UTR	Exon 10 of 10	NP_899233.1	Q16515-2
	ASIC2	NM_001094.5		c.*301G>A		3_prime_UTR	Exon 10 of 10	NP_001085.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	ENST00000225823.7	TSL:1 MANE Select	c.*301G>A		3_prime_UTR	Exon 10 of 10	ENSP00000225823.2	Q16515-2
	ASIC2	ENST00000359872.6	TSL:1	c.*301G>A		3_prime_UTR	Exon 10 of 10	ENSP00000352934.6	Q16515-1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 69058 AN: 151958 Hom.: 18026 Cov.: 32

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.459

GnomAD4 exome AF: 0.373 AC: 90105 AN: 241774 Hom.: 18204 Cov.: 0 AF XY: 0.373 AC XY: 46604 AN XY: 124858

African (AFR) AF: 0.725 AC: 6106 AN: 8426

American (AMR) AF: 0.271 AC: 3370 AN: 12454

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 3143 AN: 7636

East Asian (EAS) AF: 0.463 AC: 7933 AN: 17116

South Asian (SAS) AF: 0.379 AC: 9140 AN: 24114

European-Finnish (FIN) AF: 0.238 AC: 3150 AN: 13260

Middle Eastern (MID) AF: 0.515 AC: 554 AN: 1076

European-Non Finnish (NFE) AF: 0.356 AC: 51026 AN: 143348

Other (OTH) AF: 0.396 AC: 5683 AN: 14344

GnomAD4 genome AF: 0.455 AC: 69158 AN: 152076 Hom.: 18069 Cov.: 32 AF XY: 0.447 AC XY: 33207 AN XY: 74346

African (AFR) AF: 0.723 AC: 30021 AN: 41496

American (AMR) AF: 0.331 AC: 5057 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1479 AN: 3470

East Asian (EAS) AF: 0.436 AC: 2254 AN: 5170

South Asian (SAS) AF: 0.391 AC: 1883 AN: 4812

European-Finnish (FIN) AF: 0.236 AC: 2498 AN: 10570

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.359 AC: 24397 AN: 67962

Other (OTH) AF: 0.463 AC: 976 AN: 2108

Alfa AF: 0.395 Hom.: 23960

Bravo AF: 0.472

Asia WGS AF: 0.454 AC: 1578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.81
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: rs28933; hg19: chr17-31340682; COSMIC: COSV56772421;