Submissions for variant NM_182943.3(PLOD2):c.306T>A (p.Asp102Glu)

dbSNP: rs764056697

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000349924	SCV000441493	uncertain significance	Bruck syndrome 2	2018-01-12	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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002278538	SCV002564979	uncertain significance	Osteogenesis imperfecta	2019-05-01	criteria provided, single submitter	clinical testing
Invitae	RCV001573580	SCV003473897	uncertain significance	not provided	2024-01-24	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 102 of the PLOD2 protein (p.Asp102Glu). This variant is present in population databases (rs764056697, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PLOD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 343652). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000349924	SCV003799980	uncertain significance	Bruck syndrome 2	2022-03-11	criteria provided, single submitter	clinical testing	The PLOD2 c.306T>A; p.Asp102Glu variant (rs764056697), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 343652). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The aspartic acid at codon 102 is weakly conserved, and computational analyses predict that this variant is neutral (REVEL: 0.03). Due to limited information, the clinical significance of the p.Asp102Glu variant is uncertain at this time.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573580	SCV001799680	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001573580	SCV001971815	likely benign	not provided		no assertion criteria provided	clinical testing