17-33024103-A-G

Variant names:

• chr17-33024103-A-G
• rs16569
• NM_183377.2:c.1196-89T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183377.2(ASIC2):​c.1196-89T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,549,468 control chromosomes in the GnomAD database, including 241,704 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 0.59 (26348 hom., cov: 31)
  • Exomes 𝑓: 0.55 (215356 hom.)
• Consequence: ASIC2 NM_183377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.373
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.673 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.1196-89T>C		intron	N/A	NP_899233.1
	ASIC2	NM_001094.5		c.1043-89T>C		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.1196-89T>C		intron	N/A	ENSP00000225823.2
	ASIC2	ENST00000359872.6	TSL:1	c.1043-89T>C		intron	N/A	ENSP00000352934.6
	ASIC2	ENST00000448983.1	TSL:3	n.601-89T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88990 AN: 151804 Hom.: 26324 Cov.: 31

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.574

GnomAD4 exome AF: 0.553 AC: 772625 AN: 1397546 Hom.: 215356 AF XY: 0.552 AC XY: 382470 AN XY: 692900

African (AFR) AF: 0.626 AC: 20040 AN: 32012

American (AMR) AF: 0.771 AC: 33272 AN: 43178

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 11984 AN: 24474

East Asian (EAS) AF: 0.532 AC: 20770 AN: 39042

South Asian (SAS) AF: 0.582 AC: 47089 AN: 80972

European-Finnish (FIN) AF: 0.602 AC: 31431 AN: 52230

Middle Eastern (MID) AF: 0.496 AC: 2403 AN: 4846

European-Non Finnish (NFE) AF: 0.540 AC: 573637 AN: 1062862

Other (OTH) AF: 0.552 AC: 31999 AN: 57930

GnomAD4 genome AF: 0.586 AC: 89061 AN: 151922 Hom.: 26348 Cov.: 31 AF XY: 0.591 AC XY: 43888 AN XY: 74272

African (AFR) AF: 0.626 AC: 25936 AN: 41404

American (AMR) AF: 0.684 AC: 10454 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1700 AN: 3470

East Asian (EAS) AF: 0.563 AC: 2894 AN: 5140

South Asian (SAS) AF: 0.580 AC: 2779 AN: 4794

European-Finnish (FIN) AF: 0.604 AC: 6390 AN: 10574

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37132 AN: 67952

Other (OTH) AF: 0.569 AC: 1201 AN: 2110

Alfa AF: 0.571 Hom.: 38456

Bravo AF: 0.596

Asia WGS AF: 0.559 AC: 1946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.77
PhyloP100		0.37
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: rs16569; hg19: chr17-31351121; COSMIC: COSV56765268;