17-33066684-C-T

Variant names:

• chr17-33066684-C-T
• rs17808461
• NM_183377.2:c.987+22179G>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.987+22179G>A 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 152,124 control chromosomes in the GnomAD database, including 3,616 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 (3616 hom., cov: 32)
• Consequence: ASIC2 NM_183377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 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.987+22179G>A		intron	N/A	NP_899233.1
	ASIC2	NM_001094.5		c.834+22179G>A		intron	N/A	NP_001085.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	ENST00000225823.7	TSL:1 MANE Select	c.987+22179G>A		intron	N/A	ENSP00000225823.2
	ASIC2	ENST00000359872.6	TSL:1	c.834+22179G>A		intron	N/A	ENSP00000352934.6
	ASIC2	ENST00000448983.1	TSL:3	n.392+22179G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32147 AN: 152006 Hom.: 3609 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.316

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: 32168 AN: 152124 Hom.: 3616 Cov.: 32 AF XY: 0.212 AC XY: 15758 AN XY: 74362

African (AFR) AF: 0.152 AC: 6330 AN: 41510

American (AMR) AF: 0.184 AC: 2805 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1011 AN: 3468

East Asian (EAS) AF: 0.205 AC: 1059 AN: 5176

South Asian (SAS) AF: 0.300 AC: 1443 AN: 4808

European-Finnish (FIN) AF: 0.233 AC: 2465 AN: 10598

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16102 AN: 67966

Other (OTH) AF: 0.248 AC: 523 AN: 2112

Alfa AF: 0.230 Hom.: 17508

Bravo AF: 0.201

Asia WGS AF: 0.274 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.48
PhyloP100		0.53
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: rs17808461; hg19: chr17-31393702;