Submissions for variant NM_005529.7(HSPG2):c.4132G>A (p.Glu1378Lys)

gnomAD frequency: 0.00406  dbSNP: rs62642525

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000335667	SCV000354917	benign	Lethal Kniest-like 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	RCV000394536	SCV000354918	benign	Schwartz-Jampel 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.
Athena Diagnostics Inc	RCV000518718	SCV000613721	benign	not specified	2017-03-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757385	SCV000885586	likely benign	not provided	2017-12-31	criteria provided, single submitter	clinical testing	The c.4132G>A; p.Glu1378Lys variant (rs62642525), to our knowledge, is not reported in the medical literature, but is listed in ClinVar as benign/uncertain significance (ClinVar ID 295849). This variant is listed in the genome Aggregation Database (gnomAD) with an African population frequency of 1.4% (identified on 242 out of 17,178 chromosomes, including 2 homozygotes). The glutamic acid at position 1378 is weakly conserved, considering 12 species (Alamut software v.2.10.0), and computational analyses of the effects of the p.Glu1378Lys variant on protein structure and function do not predict deleterious changes (SIFT: tolerated, PolyPhen-2: benign, Align GVGD: Class C0). Based on the available information, the p.Glu1378Lys variant is likely to be benign.
Invitae	RCV000757385	SCV001117301	benign	not provided	2024-01-25	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003910079	SCV004721051	benign	HSPG2-related condition	2024-01-05	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).