Genetic Variant ASIC2:c.1522-118G>A (chr17-33016157-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_183377.2(ASIC2):c.1522-118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 891,490 control chromosomes in the GnomAD database, including 10,049 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 0.13 ( 1421 hom., cov: 32)

Exomes 𝑓: 0.14 ( 8628 hom. )

Consequence

ASIC2
NM_183377.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.41

Publications

3 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:

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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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_183377.2 link	c.1522-118G>A		intron_variant	Intron 8 of 9	ENST00000225823.7	NP_899233.1	Q16515-2
ASIC2	NM_001094.5 link	c.1369-118G>A		intron_variant	Intron 8 of 9		NP_001085.2	Q16515-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000225823.7 link	c.1522-118G>A		intron_variant	Intron 8 of 9	1	NM_183377.2	ENSP00000225823.2		Q16515-2
ASIC2	ENST00000359872.6 link	c.1369-118G>A		intron_variant	Intron 8 of 9	1		ENSP00000352934.6		Q16515-1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19609

AN:

152126

Hom.:

1420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0941

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0760

Gnomad FIN

AF:

0.0884

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.134

GnomAD4 exome

AF:

0.142

AC:

104835

AN:

739246

Hom.:

8628

AF XY:

0.140

AC XY:

53765

AN XY:

383376

show subpopulations

African (AFR)

AF:

0.0975

AC:

1864

AN:

19112

American (AMR)

AF:

0.0920

AC:

2784

AN:

30264

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

3578

AN:

17654

East Asian (EAS)

AF:

0.000531

AC:

AN:

33918

South Asian (SAS)

AF:

0.0862

AC:

5116

AN:

59374

European-Finnish (FIN)

AF:

0.0928

AC:

4050

AN:

43630

Middle Eastern (MID)

AF:

0.174

AC:

451

AN:

2588

European-Non Finnish (NFE)

AF:

0.164

AC:

81678

AN:

497188

Other (OTH)

AF:

0.149

AC:

5296

AN:

35518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

4310

8621

12931

17242

21552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.129

AC:

19618

AN:

152244

Hom.:

1421

Cov.:

AF XY:

0.121

AC XY:

9037

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0941

AC:

3909

AN:

41548

American (AMR)

AF:

0.110

AC:

1684

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

687

AN:

3472

East Asian (EAS)

AF:

0.00155

AC:

AN:

5176

South Asian (SAS)

AF:

0.0766

AC:

370

AN:

4828

European-Finnish (FIN)

AF:

0.0884

AC:

938

AN:

10606

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.169

AC:

11473

AN:

68006

Other (OTH)

AF:

0.133

AC:

279

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

901

1802

2702

3603

4504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.123

Hom.:

579

Bravo

AF:

0.129

Asia WGS

AF:

0.0460

AC:

162

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

0.024

(source)

DANN

Benign

0.24

PhyloP100

-3.4

Mutation Taster

=100/0

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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17-33016157-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over