5-64885498-CA-CAA
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_005869.4(CWC27):c.1002dupA(p.Val335SerfsTer13) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000151 in 1,455,696 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000015 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CWC27
NM_005869.4 frameshift
NM_005869.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.17
Publications
4 publications found
Genes affected
CWC27 (HGNC:10664): (CWC27 spliceosome associated cyclophilin) Predicted to enable peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in protein peptidyl-prolyl isomerization. Located in nucleoplasm. Part of U2-type precatalytic spliceosome and catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]
CWC27 Gene-Disease associations (from GenCC):
- metaphyseal chondrodysplasia-retinitis pigmentosa syndromeInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 5-64885498-C-CA is Pathogenic according to our data. Variant chr5-64885498-C-CA is described in ClinVar as Pathogenic. ClinVar VariationId is 426073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_005869.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CWC27 | MANE Select | c.1002dupA | p.Val335SerfsTer13 | frameshift | Exon 11 of 14 | NP_005860.2 | Q6UX04-1 | ||
| CWC27 | c.1002dupA | p.Val335SerfsTer13 | frameshift | Exon 11 of 13 | NP_001284573.1 | Q6UX04 | |||
| CWC27 | c.1002dupA | p.Val335SerfsTer13 | frameshift | Exon 11 of 12 | NP_001351407.1 | A0A8I5KUW8 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CWC27 | TSL:1 MANE Select | c.1002dupA | p.Val335SerfsTer13 | frameshift | Exon 11 of 14 | ENSP00000370460.2 | Q6UX04-1 | ||
| CWC27 | c.903dupA | p.Val302SerfsTer13 | frameshift | Exon 10 of 13 | ENSP00000509052.1 | A0A8I5KST0 | |||
| CWC27 | c.1002dupA | p.Val335SerfsTer13 | frameshift | Exon 11 of 15 | ENSP00000508653.1 | A0A8I5KX65 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 150934Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
0
AN:
150934
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
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Gnomad ASJ
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Gnomad EAS
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Gnomad SAS
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Gnomad FIN
AF:
Gnomad MID
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Gnomad NFE
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Gnomad OTH
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GnomAD2 exomes AF: 0.0000590 AC: 14AN: 237276 AF XY: 0.0000705 show subpopulations
GnomAD2 exomes
AF:
AC:
14
AN:
237276
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1455696Hom.: 0 Cov.: 31 AF XY: 0.0000221 AC XY: 16AN XY: 723408 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
22
AN:
1455696
Hom.:
Cov.:
31
AF XY:
AC XY:
16
AN XY:
723408
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
33394
American (AMR)
AF:
AC:
0
AN:
44014
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25928
East Asian (EAS)
AF:
AC:
2
AN:
39580
South Asian (SAS)
AF:
AC:
4
AN:
84894
European-Finnish (FIN)
AF:
AC:
1
AN:
53084
Middle Eastern (MID)
AF:
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
AC:
12
AN:
1108814
Other (OTH)
AF:
AC:
2
AN:
60230
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000221728), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.359
Heterozygous variant carriers
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10
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0.20
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0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
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Age
GnomAD4 genome 0.00 AC: 0AN: 150934Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 73600
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
150934
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
73600
African (AFR)
AF:
AC:
0
AN:
41050
American (AMR)
AF:
AC:
0
AN:
15138
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3456
East Asian (EAS)
AF:
AC:
0
AN:
5174
South Asian (SAS)
AF:
AC:
0
AN:
4772
European-Finnish (FIN)
AF:
AC:
0
AN:
10328
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67718
Other (OTH)
AF:
AC:
0
AN:
2072
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
4
-
-
Metaphyseal chondrodysplasia-retinitis pigmentosa syndrome (4)
1
-
-
not provided (1)
1
-
-
Retinal dystrophy (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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