rs28932

Positions:

• chr17-33013729-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183377.2(ASIC2):​c.*236A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 557,590 control chromosomes in the GnomAD database, including 632 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 0.052 (255 hom., cov: 32)
  • Exomes 𝑓: 0.037 (377 hom.)
• Consequence: ASIC2 NM_183377.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASIC2	NM_183377.2	c.*236A>G		3_prime_UTR_variant	10/10	ENST00000225823.7
ASIC2	NM_001094.5	c.*236A>G		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASIC2	ENST00000225823.7	c.*236A>G		3_prime_UTR_variant	10/10	1	NM_183377.2
ASIC2	ENST00000359872.6	c.*236A>G		3_prime_UTR_variant	10/10	1		P1

Frequencies

GnomAD3 genomes AF: 0.0520 AC: 7911 AN: 152188 Hom.: 252 Cov.: 32

Gnomad AFR AF: 0.0962

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.0451

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.0451

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0353

Gnomad OTH AF: 0.0656

GnomAD4 exome AF: 0.0366 AC: 14849 AN: 405282 Hom.: 377 Cov.: 2 AF XY: 0.0373 AC XY: 7912 AN XY: 211936

Gnomad4 AFR exome AF: 0.0988

Gnomad4 AMR exome AF: 0.0390

Gnomad4 ASJ exome AF: 0.0283

Gnomad4 EAS exome AF: 0.0199

Gnomad4 SAS exome AF: 0.0476

Gnomad4 FIN exome AF: 0.0165

Gnomad4 NFE exome AF: 0.0356

Gnomad4 OTH exome AF: 0.0435

GnomAD4 genome AF: 0.0520 AC: 7925 AN: 152308 Hom.: 255 Cov.: 32 AF XY: 0.0511 AC XY: 3807 AN XY: 74460

Gnomad4 AFR AF: 0.0962

Gnomad4 AMR AF: 0.0451

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.0266

Gnomad4 SAS AF: 0.0453

Gnomad4 FIN AF: 0.0156

Gnomad4 NFE AF: 0.0353

Gnomad4 OTH AF: 0.0649

Alfa AF: 0.0434 Hom.: 180

Bravo AF: 0.0572

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.0
DANN	Benign	0.64

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: rs28932; hg19: chr17-31340747; COSMIC: COSV105047586;