Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000464222 | SCV000541745 | likely benign | Beckwith-Wiedemann syndrome | 2024-01-21 | criteria provided, single submitter | clinical testing | |
University of Washington Department of Laboratory Medicine, |
RCV000664304 | SCV000788233 | benign | IMAGe syndrome; Beckwith-Wiedemann syndrome due to CDKN1C mutation | 2018-04-01 | criteria provided, single submitter | research | The CDKN1C variant designated as NM_000076.2:c.353C>T (p.Pro118Leu) is classified as likely benign. The CDKN1C gene is a paternally imprinted gene. Maternally inherited pathogenic variants in the CDKN1C gene are associated with Beckwith-Wiedemann syndrome and IMAGE syndrome. However, missense variants associated with these syndromes are in different domains than the CDKN1C p.Pro118Leu missense variant (Arboleda et al 2012, PMID:22634751), indicating that this variant is less likely to cause disease. Additionally, the variant was maternally inherited in one observed patient who reported no clinical symptoms of Beckwith-Wiedemann syndrome or IMAGE syndrome after four decades of life. Bayesian analysis integrating this data (Tavtigian et al, 2018, PMID:29300386) gives less than 0.1% probability of pathogenicity, which is consistent with a classification of benign. This analysis was performed in conjunction with the family studies project as part of the University of Washington Find My Variant Study. |
Sema4, |
RCV000464222 | SCV002534267 | likely benign | Beckwith-Wiedemann syndrome | 2021-06-03 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002526393 | SCV003717965 | likely benign | Inborn genetic diseases | 2021-06-14 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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. |
Prevention |
RCV003899902 | SCV004712279 | likely benign | CDKN1C-related condition | 2024-02-22 | criteria provided, single submitter | 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). |