rs16569

chr17-33024103-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASIC2	NM_183377.2	c.1196-89T>C		intron_variant		ENST00000225823.7
ASIC2	NM_001094.5	c.1043-89T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASIC2	ENST00000225823.7	c.1196-89T>C		intron_variant		1	NM_183377.2
ASIC2	ENST00000359872.6	c.1043-89T>C		intron_variant		1		P1
ASIC2	ENST00000448983.1	n.601-89T>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.626

Gnomad4 AMR exome AF: 0.771

Gnomad4 ASJ exome AF: 0.490

Gnomad4 EAS exome AF: 0.532

Gnomad4 SAS exome AF: 0.582

Gnomad4 FIN exome AF: 0.602

Gnomad4 NFE exome AF: 0.540

Gnomad4 OTH exome AF: 0.552

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

Gnomad4 AFR AF: 0.626

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.569

Alfa AF: 0.557 Hom.: 24037

Bravo AF: 0.596

Asia WGS AF: 0.559 AC: 1946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.4
Dann	Benign	0.77

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: rs16569; hg19: chr17-31351121; COSMIC: COSV56765268;