ClinVar Miner

Submissions for variant NM_133459.4(CCBE1):c.310G>A (p.Asp104Asn)

gnomAD frequency: 0.00006  dbSNP: rs139165727
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital RCV001848602 SCV002104277 pathogenic See cases criteria provided, single submitter clinical testing The CCBE1 c.310G>A variant replaces the aspartic acid with asparagine at amino acid position 104 of the protein. This variant has been found at a low frequency in a large population cohort, primarily in individuals with European ancestry (Gnomad v21.1, European: 36 of 129,054 alleles, 0.03%, no homozygous individuals reported). The majority of in silico tools predict that the c.310G>A variant has a damaging impact on protein function and functional studies are consistent with a loss of function effect (PMID: 27345729).
Labcorp Genetics (formerly Invitae), Labcorp RCV002034768 SCV002184076 uncertain significance not provided 2022-08-21 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 104 of the CCBE1 protein (p.Asp104Asn). This variant is present in population databases (rs139165727, gnomAD 0.03%). This missense change has been observed in individual(s) with Hennekam lymphangiectasia-lymphedema syndrome, generalized lymphatic dysplasia, and lymphedema-cholestasis syndrome (PMID: 22239599, 27345729, 28073151). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1344506). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects CCBE1 function (PMID: 27345729). 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.

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