ClinVar Miner

Submissions for variant NM_001122630.2(CDKN1C):c.736G>T (p.Ala246Ser)

gnomAD frequency: 0.00014  dbSNP: rs754283907
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000535977 SCV000623180 uncertain significance Beckwith-Wiedemann syndrome 2024-01-15 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 257 of the CDKN1C protein (p.Ala257Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CDKN1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 454031). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CDKN1C protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Sema4, Sema4 RCV000535977 SCV002534296 uncertain significance Beckwith-Wiedemann syndrome 2021-12-08 criteria provided, single submitter curation
Fulgent Genetics, Fulgent Genetics RCV002481743 SCV002796982 uncertain significance Beckwith-Wiedemann syndrome; IMAGe syndrome 2022-04-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV002527659 SCV003722054 likely benign Inborn genetic diseases 2022-08-08 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.

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