Submissions for variant NM_182943.3(PLOD2):c.1108G>A (p.Glu370Lys)

gnomAD frequency: 0.00094  dbSNP: rs147402171

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000946770	SCV000724054	likely benign	not provided	2020-11-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000946770	SCV001092920	benign	not provided	2025-01-23	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003343946	SCV004052873	uncertain significance	Inborn genetic diseases	2023-06-16	criteria provided, single submitter	clinical testing	The c.1108G>A (p.E370K) alteration is located in exon 10 (coding exon 10) of the PLOD2 gene. This alteration results from a G to A substitution at nucleotide position 1108, causing the glutamic acid (E) at amino acid position 370 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004767436	SCV005381341	likely benign	not specified	2024-08-06	criteria provided, single submitter	clinical testing	Variant summary: PLOD2 c.1108G>A (p.Glu370Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00018 in 1491366 control chromosomes, predominantly at a frequency of 0.0034 within the African or African-American subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 3-fold of the estimated maximal expected allele frequency for a pathogenic variant in PLOD2 causing Osteogenesis Imperfecta phenotype (0.0011). To our knowledge, no occurrence of c.1108G>A in individuals affected with Osteogenesis Imperfecta and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 512915). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV003905622	SCV004722861	likely benign	PLOD2-related disorder	2022-04-14	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).