dbSNP rs28936: ASIC2:c.*593A>G (chr17-33013372-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.*593A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 154,566 control chromosomes in the GnomAD database, including 18,816 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 0.46 ( 18678 hom., cov: 33)

Exomes 𝑓: 0.30 ( 138 hom. )

Consequence

ASIC2
NM_183377.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.55

Publications

12 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_183377.2 link	c.*593A>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000225823.7	NP_899233.1
ASIC2	NM_001094.5 link	c.*593A>G		3_prime_UTR_variant	Exon 10 of 10		NP_001085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000225823.7 link	c.*593A>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_183377.2	ENSP00000225823.2
ASIC2	ENST00000359872.6 link	c.*593A>G		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000352934.6

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70328

AN:

151976

Hom.:

18634

Cov.:

show subpopulations

Gnomad AFR

AF:

0.732

Gnomad AMI

AF:

0.473

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.436

Gnomad EAS

AF:

0.452

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.239

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.365

Gnomad OTH

AF:

0.463

GnomAD4 exome

AF:

0.300

AC:

741

AN:

2472

Hom.:

138

Cov.:

AF XY:

0.316

AC XY:

406

AN XY:

1284

show subpopulations

African (AFR)

AF:

0.625

AC:

AN:

American (AMR)

AF:

0.211

AC:

153

AN:

726

Ashkenazi Jewish (ASJ)

AF:

0.625

AC:

AN:

East Asian (EAS)

AF:

0.331

AC:

AN:

124

South Asian (SAS)

AF:

0.314

AC:

AN:

156

European-Finnish (FIN)

AF:

0.150

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.330

AC:

439

AN:

1330

Other (OTH)

AF:

0.446

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.463

AC:

70429

AN:

152094

Hom.:

18678

Cov.:

AF XY:

0.456

AC XY:

33885

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.733

AC:

30394

AN:

41490

American (AMR)

AF:

0.335

AC:

5111

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.436

AC:

1508

AN:

3462

East Asian (EAS)

AF:

0.453

AC:

2343

AN:

5172

South Asian (SAS)

AF:

0.448

AC:

2155

AN:

4808

European-Finnish (FIN)

AF:

0.239

AC:

2533

AN:

10580

Middle Eastern (MID)

AF:

0.568

AC:

167

AN:

294

European-Non Finnish (NFE)

AF:

0.365

AC:

24802

AN:

67988

Other (OTH)

AF:

0.467

AC:

986

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1762

3524

5285

7047

8809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<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:

0.418

Hom.:

2053

Bravo

AF:

0.479

Asia WGS

AF:

0.495

AC:

1719

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

8.8

(source)

DANN

Benign

0.34

PhyloP100

1.5

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