ClinVar Miner

Submissions for variant NM_001286577.2(C2CD3):c.6001del (p.Cys2001fs)

gnomAD frequency: 0.00001  dbSNP: rs1398494529
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV001591677 SCV001815707 likely pathogenic Orofaciodigital syndrome type 14 2020-11-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001882709 SCV002160650 uncertain significance not provided 2022-10-17 criteria provided, single submitter clinical testing The C2CD3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_001286577.1, and corresponds to NM_015531.5:c.*439del in the primary transcript. This sequence change creates a premature translational stop signal (p.Cys2001Alafs*9) in the C2CD3 gene. While this is anticipated to result in nonsense mediated decay, it is not known whether truncations in this region of the protein cause disease. This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with C2CD3-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV001882709 SCV004847457 uncertain significance not provided 2024-02-27 criteria provided, single submitter clinical testing The p.Cys2001AlafsX9 (c.6001delT) variant in C2CD3 has not been previously reported in individuals with orofaciodigital syndrome type 14 but has been reported by other clinical laboratories in ClinVar (Variation ID 1213728). It has also been identified in 0.007% (1/15282) of Admixed American chromosomes by gnomAD (http://gnomad.broadinstitute.org, v.3.1.2). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 2001 and leads to a premature termination codon 9 amino acids downstream. This variant however is present in a transcript that is not predominantly expressed in the relevant tissues of interest and is therefore not the primary transcript for this gene. In the primary transcript (NM_015531.5), this variant occurs in the 3’UTR (c.*439). Therefore, the functional impact of this variant is unknown. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PVS1_Moderate, PM2_Supporting.

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