dbSNP rs2074215: ASIC2:c.1521+74A>G (chr17-33017531-T-C) – 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.1521+74A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 1,299,808 control chromosomes in the GnomAD database, including 201,882 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 0.60 ( 28862 hom., cov: 32)

Exomes 𝑓: 0.54 ( 173020 hom. )

Consequence

ASIC2
NM_183377.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.432

Publications

8 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 (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_183377.2 link	c.1521+74A>G		intron_variant	Intron 8 of 9	ENST00000225823.7	NP_899233.1
ASIC2	NM_001094.5 link	c.1368+74A>G		intron_variant	Intron 8 of 9		NP_001085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000225823.7 link	c.1521+74A>G		intron_variant	Intron 8 of 9	1	NM_183377.2	ENSP00000225823.2
ASIC2	ENST00000359872.6 link	c.1368+74A>G		intron_variant	Intron 8 of 9	1		ENSP00000352934.6

Frequencies

GnomAD3 genomes

AF:

0.602

AC:

91562

AN:

152060

Hom.:

28823

Cov.:

show subpopulations

Gnomad AFR

AF:

0.794

Gnomad AMI

AF:

0.593

Gnomad AMR

AF:

0.448

Gnomad ASJ

AF:

0.613

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.557

Gnomad FIN

AF:

0.513

Gnomad MID

AF:

0.668

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.592

GnomAD4 exome

AF:

0.544

AC:

624819

AN:

1147630

Hom.:

173020

AF XY:

0.545

AC XY:

316515

AN XY:

580498

show subpopulations

African (AFR)

AF:

0.806

AC:

21329

AN:

26474

American (AMR)

AF:

0.346

AC:

13699

AN:

39614

Ashkenazi Jewish (ASJ)

AF:

0.621

AC:

13805

AN:

22234

East Asian (EAS)

AF:

0.557

AC:

20793

AN:

37326

South Asian (SAS)

AF:

0.549

AC:

39773

AN:

72500

European-Finnish (FIN)

AF:

0.511

AC:

25506

AN:

49938

Middle Eastern (MID)

AF:

0.638

AC:

3188

AN:

4994

European-Non Finnish (NFE)

AF:

0.543

AC:

458559

AN:

844794

Other (OTH)

AF:

0.566

AC:

28167

AN:

49756

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

13200

26400

39599

52799

65999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11812

23624

35436

47248

59060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.602

AC:

91649

AN:

152178

Hom.:

28862

Cov.:

AF XY:

0.597

AC XY:

44405

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.794

AC:

32974

AN:

41546

American (AMR)

AF:

0.448

AC:

6847

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.613

AC:

2125

AN:

3464

East Asian (EAS)

AF:

0.526

AC:

2719

AN:

5166

South Asian (SAS)

AF:

0.557

AC:

2683

AN:

4820

European-Finnish (FIN)

AF:

0.513

AC:

5432

AN:

10584

Middle Eastern (MID)

AF:

0.670

AC:

197

AN:

294

European-Non Finnish (NFE)

AF:

0.542

AC:

36876

AN:

67980

Other (OTH)

AF:

0.594

AC:

1256

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1777

3555

5332

7110

8887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

746

1492

2238

2984

3730

<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:

0.568

Hom.:

4761

Bravo

AF:

0.604

Asia WGS

AF:

0.573

AC:

1989

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

2.2

(source)

DANN

Benign

0.34

PhyloP100

-0.43

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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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