Submissions for variant NM_006031.6(PCNT):c.6625G>A (p.Ala2209Thr)

gnomAD frequency: 0.00008  dbSNP: rs769183047

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000726079	SCV000341789	uncertain significance	not provided	2016-05-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000726079	SCV000617119	uncertain significance	not provided	2015-08-28	criteria provided, single submitter	clinical testing	The A2209T variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A2209T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002282107	SCV002570807	uncertain significance	not specified	2022-07-28	criteria provided, single submitter	clinical testing	Variant summary: PCNT c.6625G>A (p.Ala2209Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-05 in 250392 control chromosomes (gnomAD). To our knowledge, no occurrence of c.6625G>A in individuals affected with Microcephalic Osteodysplastic Primordial Dwarfism Type II and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
CeGaT Center for Human Genetics Tuebingen	RCV000726079	SCV004183949	uncertain significance	not provided	2023-11-01	criteria provided, single submitter	clinical testing	PCNT: PM2:Supporting, BP4
PreventionGenetics, part of Exact Sciences	RCV003949906	SCV004761687	uncertain significance	PCNT-related condition	2023-12-27	criteria provided, single submitter	clinical testing	The PCNT c.6625G>A variant is predicted to result in the amino acid substitution p.Ala2209Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.017% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.