NM_001384732.1:c.2611C>T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_001384732.1(CPLANE1):c.2611C>T(p.Arg871Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000244 in 1,353,702 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001384732.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CPLANE1 | NM_001384732.1 | c.2611C>T | p.Arg871Cys | missense_variant | Exon 15 of 53 | ENST00000651892.2 | NP_001371661.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CPLANE1 | ENST00000651892.2 | c.2611C>T | p.Arg871Cys | missense_variant | Exon 15 of 53 | NM_001384732.1 | ENSP00000498265.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000355 AC: 4AN: 112684Hom.: 0 AF XY: 0.0000499 AC XY: 3AN XY: 60170
GnomAD4 exome AF: 0.0000244 AC: 33AN: 1353702Hom.: 0 Cov.: 29 AF XY: 0.0000285 AC XY: 19AN XY: 667014
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Joubert syndrome 17 Pathogenic:1Other:1
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Variant classified as Pathogenic and reported on 01-22-2018 by HNL Genomics Connective Tissue Gene Tests. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. -
not provided Pathogenic:1
In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CPLANE1 protein function. ClinVar contains an entry for this variant (Variation ID: 217589). This missense change has been observed in individual(s) with Joubert syndrome (PMID: 26092869). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 871 of the CPLANE1 protein (p.Arg871Cys). -
CPLANE1-related disorder Pathogenic:1
The CPLANE1 c.2611C>T variant is predicted to result in the amino acid substitution p.Arg871Cys. This variant was reported in an individual with Joubert syndrome (Bachmann-Gagescu et al. 2015. PubMed ID: 26092869). This variant is reported in 0.016% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. This variant is interpreted as likely pathogenic. -
Orofaciodigital syndrome type 6;C3553264:Joubert syndrome 17 Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at