Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001267381 | SCV001445562 | pathogenic | Inborn genetic diseases | 2017-12-26 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001390091 | SCV001591709 | pathogenic | not provided | 2018-05-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with C5orf42-related disease. This sequence change creates a premature translational stop signal (p.Thr2755Hisfs*2) in the C5orf42 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Loss-of-function variants in C5orf42 are known to be pathogenic (PMID: 22425360). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003987663 | SCV004804160 | pathogenic | Joubert syndrome and related disorders | 2024-01-04 | criteria provided, single submitter | clinical testing | Variant summary: CPLANE1 c.8263delA (p.Thr2755HisfsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 8.2e-06 in 1460458 control chromosomes (i.e., 12 alleles, no homozygotes; gnomAD v4.0.0). This frequency is not significantly higher than estimated for a pathogenic variant in CPLANE1 causing Joubert Syndrome And Related Disorders (8.2e-06 vs 0.0015), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.8263delA in individuals affected with Joubert Syndrome And Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 567531). Based on the evidence outlined above, the variant was classified as pathogenic. |