Variant 17-33025914-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_183377.2(ASIC2):c.1195+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,608,346 control chromosomes in the GnomAD database, including 96 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 0.0081 ( 5 hom., cov: 32)

Exomes 𝑓: 0.011 ( 91 hom. )

Consequence

ASIC2
NM_183377.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.787

Variant links:

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]

ASIC2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BS2

High AC in GnomAd4 at 1227 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASIC2	NM_183377.2 linkuse as main transcript	c.1195+12G>A		intron_variant		ENST00000225823.7
ASIC2	NM_001094.5 linkuse as main transcript	c.1042+12G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ASIC2	ENST00000225823.7 linkuse as main transcript	c.1195+12G>A	intron_variant	1	NM_183377.2		Q16515-2
ASIC2	ENST00000359872.6 linkuse as main transcript	c.1042+12G>A	intron_variant	1		P1	Q16515-1
ASIC2	ENST00000448983.1 linkuse as main transcript	n.600+12G>A	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00807

AC:

1227

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00729

AC:

1788

AN:

245166

Hom.:

AF XY:

0.00740

AC XY:

981

AN XY:

132564

show subpopulations

Gnomad AFR exome

AF:

0.00263

Gnomad AMR exome

AF:

0.00745

Gnomad ASJ exome

AF:

0.00421

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.000538

Gnomad FIN exome

AF:

0.00153

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.00761

GnomAD4 exome

AF:

0.0108

AC:

15734

AN:

1456102

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

7571

AN XY:

724316

show subpopulations

Gnomad4 AFR exome

AF:

0.00205

Gnomad4 AMR exome

AF:

0.00817

Gnomad4 ASJ exome

AF:

0.00453

Gnomad4 EAS exome

AF:

0.0000763

Gnomad4 SAS exome

AF:

0.000504

Gnomad4 FIN exome

AF:

0.00193

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.00905

GnomAD4 genome

AF:

0.00806

AC:

1227

AN:

152244

Hom.:

Cov.:

AF XY:

0.00793

AC XY:

590

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00270

Gnomad4 AMR

AF:

0.0141

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00481

Hom.:

Bravo

AF:

0.00920

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.4

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over