Submissions for variant NM_000301.5(PLG):c.1259G>A (p.Gly420Asp)

gnomAD frequency: 0.00184  dbSNP: rs139071351

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000890732	SCV001034499	benign	not provided	2024-01-19	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000890732	SCV003811179	uncertain significance	not provided	2021-05-04	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000890732	SCV004158589	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	PLG: BP4, BS2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004768734	SCV005381360	likely benign	not specified	2024-08-06	criteria provided, single submitter	clinical testing	Variant summary: PLG c.1259G>A (p.Gly420Asp) results in a non-conservative amino acid change located in the Kringle domain (IPR000001) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.002 in 251314 control chromosomes in the gnomAD database, including 1 homozygotes. The observed variant frequency is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in PLG causing Plasminogen Deficiency phenotype (0.0011). To our knowledge, no occurrence of c.1259G>A in individuals affected with Plasminogen Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 717878). Based on the evidence outlined above, the variant was classified as likely benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000890732	SCV001927341	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000890732	SCV001974016	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003930785	SCV004739062	likely benign	PLG-related disorder	2020-08-04	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).