Variant chr17-33111887-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.55

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:

ENSG00000266535 (HGNC:):

ENSG00000266535 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASIC2	NM_183377.2 linkuse as main transcript	c.859+30G>A		intron_variant		ENST00000225823.7	NP_899233.1	Q16515-2
ASIC2	NM_001094.5 linkuse as main transcript	c.706+30G>A		intron_variant			NP_001085.2	Q16515-1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ASIC2	ENST00000225823.7 linkuse as main transcript	c.859+30G>A	intron_variant		1	NM_183377.2	ENSP00000225823.2	Q16515-2
ASIC2	ENST00000359872.6 linkuse as main transcript	c.706+30G>A	intron_variant		1		ENSP00000352934.6	Q16515-1
ENSG00000266535	ENST00000584688.1 linkuse as main transcript	n.30C>T	non_coding_transcript_exon_variant	1/3	4
ASIC2	ENST00000448983.1 linkuse as main transcript	n.264+30G>A	intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0827

AC:

12571

AN:

152008

Hom.:

908

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0478

AC:

11080

AN:

231588

Hom.:

529

AF XY:

0.0453

AC XY:

5616

AN XY:

124044

show subpopulations

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 SAS exome

AF:

0.0391

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.:

AF XY:

0.0379

AC XY:

27093

AN XY:

713992

show subpopulations

Gnomad4 AFR exome

AF:

0.197

Gnomad4 AMR exome

AF:

0.0323

Gnomad4 ASJ exome

AF:

0.0500

Gnomad4 EAS exome

AF:

0.00746

Gnomad4 SAS exome

AF:

0.0389

Gnomad4 FIN exome

AF:

0.0634

Gnomad4 NFE exome

AF:

0.0327

Gnomad4 OTH exome

AF:

0.0453

GnomAD4 genome

AF:

0.0827

AC:

12587

AN:

152126

Hom.:

909

Cov.:

AF XY:

0.0824

AC XY:

6129

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.0527

Gnomad4 ASJ

AF:

0.0516

Gnomad4 EAS

AF:

0.00310

Gnomad4 SAS

AF:

0.0374

Gnomad4 FIN

AF:

0.0673

Gnomad4 NFE

AF:

0.0336

Gnomad4 OTH

AF:

0.0897

Alfa

AF:

0.0471

Hom.:

172

Bravo

AF:

0.0868

Asia WGS

AF:

0.0430

AC:

150

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.73

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

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