ClinVar Miner

Submissions for variant NM_006031.6(PCNT):c.2247A>C (p.Glu749Asp)

gnomAD frequency: 0.00031  dbSNP: rs202246527
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000333587 SCV000436964 uncertain significance Microcephalic osteodysplastic primordial dwarfism type II 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genetic Services Laboratory, University of Chicago RCV000503878 SCV000596272 uncertain significance not specified 2017-02-20 criteria provided, single submitter clinical testing
Baylor Genetics RCV000333587 SCV001526073 uncertain significance Microcephalic osteodysplastic primordial dwarfism type II 2018-02-13 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Invitae RCV001861187 SCV002224948 uncertain significance not provided 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 749 of the PCNT protein (p.Glu749Asp). This variant is present in population databases (rs202246527, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with PCNT-related conditions. ClinVar contains an entry for this variant (Variation ID: 340476). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
PreventionGenetics, part of Exact Sciences RCV003392211 SCV004120973 uncertain significance PCNT-related condition 2024-01-03 criteria provided, single submitter clinical testing The PCNT c.2247A>C variant is predicted to result in the amino acid substitution p.Glu749Asp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.076% of alleles in individuals of Latino descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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