Submissions for variant NM_198129.4(LAMA3):c.8445C>A (p.Asn2815Lys)

gnomAD frequency: 0.17201  dbSNP: rs1154232

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000250312	SCV000303062	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000264313	SCV000407995	benign	Laryngo-onycho-cutaneous syndrome	2018-01-13	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000328887	SCV000407996	benign	Junctional epidermolysis bullosa gravis of Herlitz	2018-01-13	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000250312	SCV000539496	benign	not specified	2016-03-29	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000250312	SCV001361865	benign	not specified	2019-05-16	criteria provided, single submitter	clinical testing	Variant summary: LAMA3 c.3618C>A (p.Asn1206Lys) 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 0.19 in 251140 control chromosomes, predominantly at a frequency of 0.24 within the South Asian subpopulation in the gnomAD database, including 894 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 531 fold of the estimated maximal expected allele frequency for a pathogenic variant in LAMA3 causing Junctional Epidermolysis Bullosa phenotype (0.00045), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. c.3618C>A has been reported in the literature in individuals affected with atopic dermatitis and also in the control population (Stemmler_2014). This report does not provide unequivocal conclusions about association of the variant with Junctional Epidermolysis Bullosa . To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001518011	SCV001726636	benign	not provided	2025-01-29	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001542966	SCV001761394	benign	Junctional epidermolysis bullosa, non-Herlitz type	2021-07-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000328887	SCV001761395	benign	Junctional epidermolysis bullosa gravis of Herlitz	2021-07-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000264313	SCV001761396	benign	Laryngo-onycho-cutaneous syndrome	2021-07-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001518011	SCV001939606	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001518011	SCV005254069	benign	not provided		criteria provided, single submitter	not provided