chr17-33413163-G-A

Variant summary

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

The ENST00000359872.6(ASIC2):​c.556-301096C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,034 control chromosomes in the GnomAD database, including 6,738 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 0.27 ( 6738 hom., cov: 32)

Consequence

ASIC2
ENST00000359872.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.936

Publications

5 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]

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=-0.82).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASIC2NM_001094.5 linkc.556-301096C>T intron_variant Intron 1 of 9 NP_001085.2 Q16515-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASIC2ENST00000359872.6 linkc.556-301096C>T intron_variant Intron 1 of 9 1 ENSP00000352934.6 Q16515-1

Frequencies

GnomAD3 genomes
AF:
0.266
AC:
40389
AN:
151916
Hom.:
6740
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0666
Gnomad AMI
AF:
0.501
Gnomad AMR
AF:
0.288
Gnomad ASJ
AF:
0.254
Gnomad EAS
AF:
0.183
Gnomad SAS
AF:
0.312
Gnomad FIN
AF:
0.416
Gnomad MID
AF:
0.293
Gnomad NFE
AF:
0.359
Gnomad OTH
AF:
0.266
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.266
AC:
40390
AN:
152034
Hom.:
6738
Cov.:
32
AF XY:
0.268
AC XY:
19885
AN XY:
74280
show subpopulations
African (AFR)
AF:
0.0664
AC:
2755
AN:
41508
American (AMR)
AF:
0.288
AC:
4396
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.254
AC:
880
AN:
3470
East Asian (EAS)
AF:
0.183
AC:
944
AN:
5156
South Asian (SAS)
AF:
0.312
AC:
1500
AN:
4804
European-Finnish (FIN)
AF:
0.416
AC:
4390
AN:
10552
Middle Eastern (MID)
AF:
0.291
AC:
85
AN:
292
European-Non Finnish (NFE)
AF:
0.359
AC:
24428
AN:
67952
Other (OTH)
AF:
0.264
AC:
556
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1396
2792
4189
5585
6981
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
426
852
1278
1704
2130
<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:
0.322
Hom.:
14658
Bravo
AF:
0.245
Asia WGS
AF:
0.194
AC:
677
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
7.0
DANN
Benign
0.85
PhyloP100
0.94
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12941510; hg19: chr17-31740181; COSMIC: COSV63330867; API