Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000172098 | SCV000054721 | uncertain significance | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Athena Diagnostics | RCV000172098 | SCV000843424 | likely benign | not provided | 2018-06-29 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002054033 | SCV002433667 | likely benign | Alzheimer disease 4 | 2024-06-04 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002469043 | SCV002766040 | uncertain significance | not specified | 2022-11-11 | criteria provided, single submitter | clinical testing | Variant summary: PSEN2 c.166G>A (p.Gly56Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00019 in 282204 control chromosomes (gnomAD). c.166G>A has been reported in the literature in individuals affected with Parkinson Disease (Ibanez_2018) and Alzheimer Disease (Shim_2022). These reports do not provide unequivocal conclusions about association of the variant with Alzheimer Disease 4. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters have assessed the variants since 2014: all classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Prevention |
RCV003927573 | SCV004741615 | likely benign | PSEN2-related disorder | 2022-08-24 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |