17-33111887-C-T

Variant names:

• chr17-33111887-C-T
• rs9916605
• NM_183377.2:c.859+30G>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.859+30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 1,591,908 control chromosomes in the GnomAD database, including 2,487 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 0.083 (909 hom., cov: 32)
  • Exomes 𝑓: 0.038 (1578 hom.)
• Consequence: ASIC2 NM_183377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55
• 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]

ENSG00000266535 (HGNC:58564):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	NM_183377.2	MANE Select	c.859+30G>A		intron	N/A	NP_899233.1	Q16515-2
	ASIC2	NM_001094.5		c.706+30G>A		intron	N/A	NP_001085.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	ENST00000225823.7	TSL:1 MANE Select	c.859+30G>A		intron	N/A	ENSP00000225823.2	Q16515-2
	ASIC2	ENST00000359872.6	TSL:1	c.706+30G>A		intron	N/A	ENSP00000352934.6	Q16515-1
	ENSG00000266535	ENST00000584688.1	TSL:4	n.30C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0827 AC: 12571 AN: 152008 Hom.: 908 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0527

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.00310

Gnomad SAS AF: 0.0374

Gnomad FIN AF: 0.0673

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0336

Gnomad OTH AF: 0.0877

GnomAD2 exomes AF: 0.0478 AC: 11080 AN: 231588 AF XY: 0.0453

Gnomad AFR exome AF: 0.202

Gnomad AMR exome AF: 0.0299

Gnomad ASJ exome AF: 0.0520

Gnomad EAS exome AF: 0.00472

Gnomad FIN exome AF: 0.0658

Gnomad NFE exome AF: 0.0354

Gnomad OTH exome AF: 0.0499

GnomAD4 exome AF: 0.0382 AC: 54948 AN: 1439782 Hom.: 1578 Cov.: 30 AF XY: 0.0379 AC XY: 27093 AN XY: 713992

African (AFR) AF: 0.197 AC: 6512 AN: 33088

American (AMR) AF: 0.0323 AC: 1395 AN: 43208

Ashkenazi Jewish (ASJ) AF: 0.0500 AC: 1223 AN: 24442

East Asian (EAS) AF: 0.00746 AC: 292 AN: 39132

South Asian (SAS) AF: 0.0389 AC: 3171 AN: 81424

European-Finnish (FIN) AF: 0.0634 AC: 3340 AN: 52678

Middle Eastern (MID) AF: 0.0689 AC: 369 AN: 5356

European-Non Finnish (NFE) AF: 0.0327 AC: 35952 AN: 1100968

Other (OTH) AF: 0.0453 AC: 2694 AN: 59486

GnomAD4 genome AF: 0.0827 AC: 12587 AN: 152126 Hom.: 909 Cov.: 32 AF XY: 0.0824 AC XY: 6129 AN XY: 74376

African (AFR) AF: 0.196 AC: 8113 AN: 41440

American (AMR) AF: 0.0527 AC: 807 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0516 AC: 179 AN: 3470

East Asian (EAS) AF: 0.00310 AC: 16 AN: 5156

South Asian (SAS) AF: 0.0374 AC: 180 AN: 4812

European-Finnish (FIN) AF: 0.0673 AC: 714 AN: 10610

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0336 AC: 2284 AN: 68024

Other (OTH) AF: 0.0897 AC: 189 AN: 2108

Alfa AF: 0.0511 Hom.: 236

Bravo AF: 0.0868

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		2.6
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: rs9916605; hg19: chr17-31438905; COSMIC: COSV56766080; COSMIC: COSV56766080;