ClinVar Miner

Submissions for variant NM_001378615.1(CC2D2A):c.298A>C (p.Met100Leu)

gnomAD frequency: 0.00004  dbSNP: rs370014549
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001370586 SCV001567107 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-03-11 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 100 of the CC2D2A protein (p.Met100Leu). This variant is present in population databases (rs370014549, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CC2D2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1061071). 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 CC2D2A protein function. 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.
GeneDx RCV001776230 SCV002013534 uncertain significance not provided 2023-05-09 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002488165 SCV002784874 uncertain significance Meckel syndrome, type 6; Joubert syndrome 9; COACH syndrome 2; Retinitis pigmentosa 93 2024-05-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV003169907 SCV003869332 uncertain significance Inborn genetic diseases 2023-01-18 criteria provided, single submitter clinical testing The c.298A>C (p.M100L) alteration is located in exon 6 (coding exon 4) of the CC2D2A gene. This alteration results from a A to C substitution at nucleotide position 298, causing the methionine (M) at amino acid position 100 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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