Submissions for variant NM_006031.6(PCNT):c.8702C>T (p.Pro2901Leu)

gnomAD frequency: 0.00054  dbSNP: rs150615481

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000997855	SCV001153606	uncertain significance	not provided	2017-08-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001143095	SCV001303596	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	RCV000997855	SCV002115596	uncertain significance	not provided	2022-09-13	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2901 of the PCNT protein (p.Pro2901Leu). This variant is present in population databases (rs150615481, gnomAD 0.07%). 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: 809312). 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: "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	RCV003396583	SCV004112169	uncertain significance	PCNT-related condition	2024-01-09	criteria provided, single submitter	clinical testing	The PCNT c.8702C>T variant is predicted to result in the amino acid substitution p.Pro2901Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.071% of alleles in individuals of European (Non-Finnish) descent in gnomAD, which may be too common to be an unreported 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.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000997855	SCV002035364	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000997855	SCV002037796	likely benign	not provided		no assertion criteria provided	clinical testing