ClinVar Miner

Submissions for variant NM_006031.6(PCNT):c.8672C>T (p.Ala2891Val)

gnomAD frequency: 0.00032  dbSNP: rs144963695
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000147226 SCV000194593 uncertain significance Microcephalic osteodysplastic primordial dwarfism type II 2014-07-21 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000147226 SCV001303595 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.
Invitae RCV001849990 SCV002311620 uncertain significance not provided 2024-01-08 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2891 of the PCNT protein (p.Ala2891Val). This variant is present in population databases (rs144963695, gnomAD 0.1%). 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: 159674). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Preventiongenetics, part of Exact Sciences RCV003398791 SCV004111603 uncertain significance PCNT-related condition 2023-09-28 criteria provided, single submitter clinical testing The PCNT c.8672C>T variant is predicted to result in the amino acid substitution p.Ala2891Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.12% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/21-47852050-C-T), which is likely too common to be a primary cause of disease. 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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