Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000731228 | SCV000859016 | uncertain significance | not provided | 2017-12-28 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002507296 | SCV002800154 | uncertain significance | Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome | 2021-09-03 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003987686 | SCV004803634 | uncertain significance | not specified | 2024-01-22 | criteria provided, single submitter | clinical testing | Variant summary: NOTCH2 c.2677G>A (p.Gly893Ser) results in a non-conservative amino acid change located in the EGF-like domain (IPR000742) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251424 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2677G>A in individuals affected with Hajdu-Cheney Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 595624). Based on the evidence outlined above, the variant was classified as uncertain significance. |