Submissions for variant NM_005562.3(LAMC2):c.2422C>G (p.Pro808Ala)

gnomAD frequency: 0.00439  dbSNP: rs144355456

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000953011	SCV001099555	benign	not provided	2024-12-16	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001102467	SCV001259138	benign	Junctional epidermolysis bullosa	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001844248	SCV002103781	benign	not specified	2022-02-28	criteria provided, single submitter	clinical testing	Variant summary: LAMC2 c.2422C>G (p.Pro808Ala) results in a non-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 0.0049 in 251224 control chromosomes in the gnomAD database, including 7 homozygotes. The observed variant frequency is approximately 5.7 fold of the estimated maximal expected allele frequency for a pathogenic variant in LAMC2 causing Junctional Epidermolysis Bullosa phenotype (0.00087), strongly suggesting that the variant is benign. To our knowledge, no penetrant association of c.2422C>G in individuals affected with Junctional Epidermolysis Bullosa and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV000953011	SCV004123948	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	LAMC2: BP4, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV000953011	SCV005284768	benign	not provided		criteria provided, single submitter	not provided