ClinVar Miner

Submissions for variant NM_006031.6(PCNT):c.8956G>A (p.Ala2986Thr)

dbSNP: rs201877661
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000503956 SCV000596327 uncertain significance not specified 2016-03-25 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001286076 SCV001472599 uncertain significance Microcephalic osteodysplastic primordial dwarfism type II 2020-02-16 criteria provided, single submitter clinical testing The PCNT c.8956G>A; p.Ala2986Thr variant (rs201877661), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 436229). This variant is found in the Latino population with an overall allele frequency of 0.06% (21/34318 alleles) in the Genome Aggregation Database. The alanine at codon 2986 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Furthermore, only truncating variants in PCNT have been associated with disease (Rauch 2008, Willems 2010). Based on available information, this variant is considered to be likely benign. References: Rauch A et al. Mutations in the pericentrin (PCNT) gene cause primordial dwarfism. Science. 2008 Feb 8;319(5864):816-9. Willems M et al. Molecular analysis of pericentrin gene (PCNT) in a series of 24 Seckel/microcephalic osteodysplastic primordial dwarfism type II (MOPD II) families. J Med Genet. 2010 Dec;47(12):797-802.
Invitae RCV001857145 SCV002206043 uncertain significance not provided 2021-11-16 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2986 of the PCNT protein (p.Ala2986Thr). This variant is present in population databases (rs201877661, gnomAD 0.06%). 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: 436229). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine 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.

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