chr17-33047112-G-A

Position:

• chr17-33047112-G-A

Variant summary

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

The NM_183377.2(ASIC2):​c.988-18720C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,196 control chromosomes in the GnomAD database, including 3,732 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 0.21 (3732 hom., cov: 33)
• Consequence: ASIC2 NM_183377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASIC2	NM_183377.2	c.988-18720C>T		intron_variant		ENST00000225823.7
ASIC2	NM_001094.5	c.835-18720C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASIC2	ENST00000225823.7	c.988-18720C>T		intron_variant		1	NM_183377.2
ASIC2	ENST00000359872.6	c.835-18720C>T		intron_variant		1		P1
ASIC2	ENST00000448983.1	n.393-18720C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32127 AN: 152078 Hom.: 3725 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.242

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.211 AC: 32146 AN: 152196 Hom.: 3732 Cov.: 33 AF XY: 0.213 AC XY: 15811 AN XY: 74400

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.249

Alfa AF: 0.109 Hom.: 160

Bravo AF: 0.200

Asia WGS AF: 0.328 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.97
DANN	Benign	0.58

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: rs16588; hg19: chr17-31374130;