rs16561

Variant names:

• chr17-33038734-C-T
• rs16561
• NM_183377.2:c.988-10342G>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.988-10342G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,038 control chromosomes in the GnomAD database, including 21,607 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 0.52 (21607 hom., cov: 32)
• Consequence: ASIC2 NM_183377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 4 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 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.988-10342G>A		intron	N/A	NP_899233.1
	ASIC2	NM_001094.5		c.835-10342G>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.988-10342G>A		intron	N/A	ENSP00000225823.2
	ASIC2	ENST00000359872.6	TSL:1	c.835-10342G>A		intron	N/A	ENSP00000352934.6
	ASIC2	ENST00000448983.1	TSL:3	n.393-10342G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78547 AN: 151920 Hom.: 21555 Cov.: 32

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.517 AC: 78649 AN: 152038 Hom.: 21607 Cov.: 32 AF XY: 0.518 AC XY: 38498 AN XY: 74298

African (AFR) AF: 0.697 AC: 28910 AN: 41480

American (AMR) AF: 0.608 AC: 9285 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1280 AN: 3472

East Asian (EAS) AF: 0.499 AC: 2580 AN: 5170

South Asian (SAS) AF: 0.426 AC: 2055 AN: 4822

European-Finnish (FIN) AF: 0.424 AC: 4473 AN: 10538

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.419 AC: 28499 AN: 67964

Other (OTH) AF: 0.498 AC: 1053 AN: 2114

Alfa AF: 0.450 Hom.: 8972

Bravo AF: 0.542

Asia WGS AF: 0.482 AC: 1678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.8
DANN	Benign	0.54
PhyloP100		0.085
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: rs16561; hg19: chr17-31365752;