Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000145518 | SCV000192606 | benign | not specified | 2013-02-08 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001531130 | SCV001746108 | likely benign | not provided | 2021-04-01 | criteria provided, single submitter | clinical testing | |
Victorian Clinical Genetics Services, |
RCV002470772 | SCV002767285 | likely benign | Developmental and epileptic encephalopathy, 2 | 2019-08-28 | criteria provided, single submitter | clinical testing | A heterozygous missense variant, NM_003159.2(CDKL5):c.1400A>G, has been identified in exon 12 of 21 of the CDKL5 gene. The variant is predicted to result in a minor amino acid change from His to Arg at position 467 of the protein (NP_003150.1(CDKL5):p.(His467Arg)). The His residue at this position has high conservation (100 vertebrates, UCSC), but is not located within a well established functional domain. In-silico predictions for this variant are consistently pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD database at a frequency of 0.0005% (1 heterozyogte, 0 homozygotes, 0 hemizygoutes). The variant has been previously described as benign and segregated with disease in one family with disease (ClinVar, RettBASE, Evans et al 2005)). A different variant in the same codon resulting in a change to proline has also been reported as VUS (ClinVar, RettBASE, Liang et al 2011)). Based on the information available at the time of curation, this variant has been classified as LIKELY BENIGN. |
Rett |
RCV000145518 | SCV000222277 | likely benign | not specified | 2014-05-09 | no assertion criteria provided | curation | Likely benign variation, found in normal female carrier; reported as c.1399A>G, but should be c.1400A>G; in silico predictions: SIFT = deleterious, MutationTaster = disease-causing, PolyPhen2 = probably damaging, AlignGVGD = C25 |