chr17-33013372-T-C

Variant names:

• chr17-33013372-T-C
• rs28936
• NM_183377.2:c.*593A>G

Variant summary

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

The NM_183377.2(ASIC2):​c.*593A>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 0.46 in 154,566 control chromosomes in the GnomAD database, including 18,816 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 0.46 (18678 hom., cov: 33)
  • Exomes 𝑓: 0.30 (138 hom.)
• Consequence: ASIC2 NM_183377.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_183377.2	c.*593A>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000225823.7	NP_899233.1
ASIC2	NM_001094.5	c.*593A>G		3_prime_UTR_variant	Exon 10 of 10		NP_001085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000225823	c.*593A>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_183377.2	ENSP00000225823.2
ASIC2	ENST00000359872	c.*593A>G		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000352934.6

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70328 AN: 151976 Hom.: 18634 Cov.: 33

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.463

GnomAD4 exome AF: 0.300 AC: 741 AN: 2472 Hom.: 138 Cov.: 0 AF XY: 0.316 AC XY: 406 AN XY: 1284

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.625

Gnomad4 EAS exome AF: 0.331

Gnomad4 SAS exome AF: 0.314

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.446

GnomAD4 genome AF: 0.463 AC: 70429 AN: 152094 Hom.: 18678 Cov.: 33 AF XY: 0.456 AC XY: 33885 AN XY: 74330

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.467

Alfa AF: 0.407 Hom.: 1861

Bravo AF: 0.479

Asia WGS AF: 0.495 AC: 1719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.8
DANN	Benign	0.34

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: rs28936; hg19: chr17-31340390;