Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003235063 | SCV003933681 | benign | CDKL5 disorder | 2023-04-14 | reviewed by expert panel | curation | The allele frequency of the p.Pro852Leu variant in CDKL5 is 0.031% in African sub population in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). In summary, the p.Pro852Leu variant in CDKL5 is classified as benign based on the ACMG/AMP criteria (BA1). |
Gene |
RCV000144835 | SCV000191074 | likely benign | not provided | 2020-04-10 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001053868 | SCV001218151 | likely benign | Developmental and epileptic encephalopathy, 2; Angelman syndrome-like | 2025-01-23 | criteria provided, single submitter | clinical testing | |
Neuberg Centre For Genomic Medicine, |
RCV003338420 | SCV004047103 | uncertain significance | Developmental and epileptic encephalopathy, 2 | criteria provided, single submitter | clinical testing | The missense variant c.2555C>T (p.Pro852Leu) in CDKL5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant has been reported to the ClinVar database with conflicting interpretations of pathogenicity as Likely Benign/Uncertain Significance. The p.Pro852Leu variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid Pro at position 852 is changed to a Leu changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by SIFT and the residue is conserved across species. The amino acid change p.Pro852Leu in CDKL5 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. | |
Ambry Genetics | RCV004975294 | SCV005559207 | likely benign | Inborn genetic diseases | 2024-08-10 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |