chr17-33013729-T-C

Variant names:

• chr17-33013729-T-C
• rs28932
• NM_183377.2:c.*236A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0937 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	NM_183377.2	MANE Select	c.*236A>G		3_prime_UTR	Exon 10 of 10	NP_899233.1
	ASIC2	NM_001094.5		c.*236A>G		3_prime_UTR	Exon 10 of 10	NP_001085.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	ENST00000225823.7	TSL:1 MANE Select	c.*236A>G		3_prime_UTR	Exon 10 of 10	ENSP00000225823.2
	ASIC2	ENST00000359872.6	TSL:1	c.*236A>G		3_prime_UTR	Exon 10 of 10	ENSP00000352934.6

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

African (AFR) AF: 0.0988 AC: 1159 AN: 11732

American (AMR) AF: 0.0390 AC: 689 AN: 17646

Ashkenazi Jewish (ASJ) AF: 0.0283 AC: 353 AN: 12484

East Asian (EAS) AF: 0.0199 AC: 580 AN: 29212

South Asian (SAS) AF: 0.0476 AC: 1845 AN: 38738

European-Finnish (FIN) AF: 0.0165 AC: 453 AN: 27388

Middle Eastern (MID) AF: 0.0516 AC: 92 AN: 1782

European-Non Finnish (NFE) AF: 0.0356 AC: 8649 AN: 242658

Other (OTH) AF: 0.0435 AC: 1029 AN: 23642

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

African (AFR) AF: 0.0962 AC: 3998 AN: 41554

American (AMR) AF: 0.0451 AC: 690 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 91 AN: 3472

East Asian (EAS) AF: 0.0266 AC: 138 AN: 5184

South Asian (SAS) AF: 0.0453 AC: 219 AN: 4832

European-Finnish (FIN) AF: 0.0156 AC: 166 AN: 10620

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0353 AC: 2402 AN: 68024

Other (OTH) AF: 0.0649 AC: 137 AN: 2112

Alfa AF: 0.0443 Hom.: 500

Bravo AF: 0.0572

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.0
DANN	Benign	0.64
PhyloP100		-0.76
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: rs28932; hg19: chr17-31340747; COSMIC: COSV105047586;