dbSNP rs62068265: ASIC2:c.*519C>G (chr17-33013446-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_183377.2(ASIC2):c.*519C>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 0.0259 in 154,208 control chromosomes in the GnomAD database, including 80 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 0.026 ( 79 hom., cov: 33)

Exomes 𝑓: 0.027 ( 1 hom. )

Consequence

ASIC2
NM_183377.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.200

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=-0.79).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0259 (3941/152314) while in subpopulation NFE AF = 0.0404 (2746/68040). AF 95% confidence interval is 0.0391. There are 79 homozygotes in GnomAd4. There are 1914 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 3941 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_183377.2 link	c.*519C>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000225823.7	NP_899233.1
ASIC2	NM_001094.5 link	c.*519C>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.*519C>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_183377.2	ENSP00000225823.2
ASIC2	ENST00000359872.6 link	c.*519C>G		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000352934.6

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

3941

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00685

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00663

Gnomad FIN

AF:

0.0541

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0403

Gnomad OTH

AF:

0.0182

GnomAD4 exome

AF:

0.0275

AC:

AN:

1894

Hom.:

Cov.:

AF XY:

0.0217

AC XY:

AN XY:

1016

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00952

AC:

AN:

420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0116

AC:

AN:

172

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0436

AC:

AN:

298

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0393

AC:

AN:

840

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0259

AC:

3941

AN:

152314

Hom.:

Cov.:

AF XY:

0.0257

AC XY:

1914

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00681

AC:

283

AN:

41570

American (AMR)

AF:

0.0131

AC:

201

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0130

AC:

AN:

3468

East Asian (EAS)

AF:

0.00155

AC:

AN:

5170

South Asian (SAS)

AF:

0.00663

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0541

AC:

575

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0404

AC:

2746

AN:

68040

Other (OTH)

AF:

0.0180

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

198

396

595

793

991

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0345

Hom.:

Bravo

AF:

0.0217

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

9.9

(source)

DANN

Benign

0.74

PhyloP100

0.20

Mutation Taster

=100/0

polymorphism

(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