dbSNP rs28935: ASIC2:c.*539T>C (chr17-33013426-A-G) – 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.*539T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 154,990 control chromosomes in the GnomAD database, including 4,983 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 0.23 ( 4940 hom., cov: 33)

Exomes 𝑓: 0.16 ( 43 hom. )

Consequence

ASIC2
NM_183377.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.43

Publications

7 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:

Genome browser will be placed here

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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_183377.2 link	c.*539T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000225823.7	NP_899233.1	Q16515-2
ASIC2	NM_001094.5 link	c.*539T>C		3_prime_UTR_variant	Exon 10 of 10		NP_001085.2	Q16515-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000225823.7 link	c.*539T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_183377.2	ENSP00000225823.2		Q16515-2
ASIC2	ENST00000359872.6 link	c.*539T>C		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000352934.6		Q16515-1

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

35016

AN:

152032

Hom.:

4919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.378

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.280

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.223

GnomAD4 exome

AF:

0.158

AC:

449

AN:

2840

Hom.:

Cov.:

AF XY:

0.151

AC XY:

227

AN XY:

1500

show subpopulations

African (AFR)

AF:

0.300

AC:

AN:

American (AMR)

AF:

0.126

AC:

AN:

762

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

AN:

East Asian (EAS)

AF:

0.271

AC:

AN:

210

South Asian (SAS)

AF:

0.262

AC:

AN:

164

European-Finnish (FIN)

AF:

0.111

AC:

AN:

162

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.152

AC:

215

AN:

1416

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.231

AC:

35089

AN:

152150

Hom.:

4940

Cov.:

AF XY:

0.232

AC XY:

17279

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.379

AC:

15728

AN:

41498

American (AMR)

AF:

0.160

AC:

2454

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

712

AN:

3468

East Asian (EAS)

AF:

0.422

AC:

2176

AN:

5162

South Asian (SAS)

AF:

0.278

AC:

1342

AN:

4826

European-Finnish (FIN)

AF:

0.133

AC:

1409

AN:

10606

Middle Eastern (MID)

AF:

0.276

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.155

AC:

10551

AN:

67974

Other (OTH)

AF:

0.229

AC:

485

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1307

2613

3920

5226

6533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.185

Hom.:

1285

Bravo

AF:

0.235

Asia WGS

AF:

0.391

AC:

1357

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.71

(source)

DANN

Benign

0.45

PhyloP100

-1.4

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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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