rs1554709677
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1_StrongPM2PP3PP5_Moderate
The NM_000067.3(CA2):c.21C>A(p.Tyr7*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CA2
NM_000067.3 stop_gained
NM_000067.3 stop_gained
Scores
2
3
1
Clinical Significance
Conservation
PhyloP100: 1.62
Publications
0 publications found
Genes affected
CA2 (HGNC:1373): (carbonic anhydrase 2) The protein encoded by this gene is one of several isozymes of carbonic anhydrase, which catalyzes reversible hydration of carbon dioxide. Defects in this enzyme are associated with osteopetrosis and renal tubular acidosis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 9 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 17 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
Variant 8-85464102-C-A is Pathogenic according to our data. Variant chr8-85464102-C-A is described in ClinVar as Pathogenic. ClinVar VariationId is 522744.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000067.3. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CA2 | TSL:1 MANE Select | c.21C>A | p.Tyr7* | stop_gained | Exon 1 of 7 | ENSP00000285379.4 | P00918 | ||
| CA2 | c.21C>A | p.Tyr7* | stop_gained | Exon 1 of 7 | ENSP00000630089.1 | ||||
| CA2 | TSL:2 | n.92C>A | non_coding_transcript_exon | Exon 1 of 3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1395240Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 689284
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1395240
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
689284
African (AFR)
AF:
AC:
0
AN:
30758
American (AMR)
AF:
AC:
0
AN:
36264
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25030
East Asian (EAS)
AF:
AC:
0
AN:
35642
South Asian (SAS)
AF:
AC:
0
AN:
79056
European-Finnish (FIN)
AF:
AC:
0
AN:
43828
Middle Eastern (MID)
AF:
AC:
0
AN:
5676
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1080980
Other (OTH)
AF:
AC:
0
AN:
58006
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Osteopetrosis with renal tubular acidosis (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
PhyloP100
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -4
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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