5-37226775-TA-TAA
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001384732.1(CPLANE1):c.1819dupT(p.Tyr607LeufsTer12) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000117 in 1,539,920 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
CPLANE1
NM_001384732.1 frameshift
NM_001384732.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.24
Publications
8 publications found
Genes affected
CPLANE1 (HGNC:25801): (ciliogenesis and planar polarity effector complex subunit 1) The protein encoded by this gene has putative coiled-coil domains and may be a transmembrane protein. Defects in this gene are a cause of Joubert syndrome (JBTS). [provided by RefSeq, May 2012]
CPLANE1 Gene-Disease associations (from GenCC):
- Joubert syndrome 17Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, ClinGen, G2P, Illumina, Labcorp Genetics (formerly Invitae)
- orofaciodigital syndrome type 6Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
- Joubert syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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 5-37226775-T-TA is Pathogenic according to our data. Variant chr5-37226775-T-TA is described in ClinVar as Pathogenic. ClinVar VariationId is 194120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001384732.1. 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 |
|---|---|---|---|---|---|---|---|---|---|
| CPLANE1 | NM_001384732.1 | MANE Select | c.1819dupT | p.Tyr607LeufsTer12 | frameshift | Exon 12 of 53 | NP_001371661.1 | ||
| CPLANE1 | NM_023073.4 | c.1819dupT | p.Tyr607LeufsTer12 | frameshift | Exon 12 of 52 | NP_075561.3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CPLANE1 | ENST00000651892.2 | MANE Select | c.1819dupT | p.Tyr607LeufsTer12 | frameshift | Exon 12 of 53 | ENSP00000498265.2 | ||
| CPLANE1 | ENST00000955438.1 | c.1819dupT | p.Tyr607LeufsTer12 | frameshift | Exon 12 of 53 | ENSP00000625497.1 | |||
| CPLANE1 | ENST00000508244.5 | TSL:5 | c.1819dupT | p.Tyr607LeufsTer12 | frameshift | Exon 11 of 51 | ENSP00000421690.1 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152060Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152060
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000122 AC: 17AN: 1387860Hom.: 0 Cov.: 32 AF XY: 0.0000161 AC XY: 11AN XY: 683960 show subpopulations
GnomAD4 exome
AF:
AC:
17
AN:
1387860
Hom.:
Cov.:
32
AF XY:
AC XY:
11
AN XY:
683960
show subpopulations
African (AFR)
AF:
AC:
1
AN:
30806
American (AMR)
AF:
AC:
1
AN:
33230
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
24708
East Asian (EAS)
AF:
AC:
0
AN:
35590
South Asian (SAS)
AF:
AC:
1
AN:
76732
European-Finnish (FIN)
AF:
AC:
1
AN:
49062
Middle Eastern (MID)
AF:
AC:
0
AN:
5620
European-Non Finnish (NFE)
AF:
AC:
9
AN:
1074644
Other (OTH)
AF:
AC:
3
AN:
57468
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.431
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
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>80
Age
GnomAD4 genome 0.00000658 AC: 1AN: 152060Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74304 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152060
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74304
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41418
American (AMR)
AF:
AC:
0
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3466
East Asian (EAS)
AF:
AC:
0
AN:
5192
South Asian (SAS)
AF:
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
AC:
0
AN:
10598
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67990
Other (OTH)
AF:
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
2
-
-
not provided (2)
1
-
-
Inborn genetic diseases (1)
1
-
-
Joubert syndrome and related disorders (1)
1
-
-
Orofaciodigital syndrome type 6;C3553264:Joubert syndrome 17 (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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