Genetic Variant ASIC2:c.556-421730C>T (chr17-33533797-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000359872.6(ASIC2):c.556-421730C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 152,146 control chromosomes in the GnomAD database, including 244 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 0.033 ( 244 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

ASIC2
ENST00000359872.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.982

Publications

0 publications found

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:

ENSG00000265125 (HGNC:27103):

ENSG00000265125 links:

AA06 (HGNC:):

AA06 links:

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ACMG classification

Classification was made for transcript

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

BP4

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

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_001094.5 link	c.556-421730C>T		intron_variant	Intron 1 of 9		NP_001085.2	Q16515-1
AA06	NR_037584.2 link	n.-37C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ASIC2	ENST00000359872.6 link	c.556-421730C>T	intron_variant	Intron 1 of 9	1	ENSP00000352934.6	Q16515-1
ENSG00000265125	ENST00000726249.1 link	n.138+9912G>A	intron_variant	Intron 1 of 3
AA06	ENST00000579745.1 link	n.-37C>T	upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0333

AC:

5066

AN:

152028

Hom.:

245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0182

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0444

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.00209

Gnomad OTH

AF:

0.0301

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0333

AC:

5069

AN:

152146

Hom.:

244

Cov.:

AF XY:

0.0324

AC XY:

2412

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.104

AC:

4324

AN:

41480

American (AMR)

AF:

0.0182

AC:

278

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00807

AC:

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5180

South Asian (SAS)

AF:

0.0445

AC:

214

AN:

4814

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00209

AC:

142

AN:

68016

Other (OTH)

AF:

0.0298

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

217

433

650

866

1083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0221

Hom.:

Bravo

AF:

0.0354

Asia WGS

AF:

0.0280

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

0.29

(source)

DANN

Benign

0.63

PhyloP100

-0.98

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over