Submissions for variant NM_005529.7(HSPG2):c.7438C>T (p.Arg2480Trp)

gnomAD frequency: 0.00016  dbSNP: rs143437991

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000179196	SCV000231403	uncertain significance	not provided	2014-10-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000370645	SCV000354777	likely benign	Schwartz-Jampel syndrome	2018-01-12	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000259625	SCV000354778	likely benign	Lethal Kniest-like syndrome	2018-01-12	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae	RCV000179196	SCV001058176	likely benign	not provided	2023-07-17	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000179196	SCV003809358	uncertain significance	not provided	2019-02-14	criteria provided, single submitter	clinical testing
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine	RCV000259625	SCV004048137	uncertain significance	Lethal Kniest-like syndrome		criteria provided, single submitter	clinical testing	The missense variant in c.7441C>T (p.Arg2481Trp) in HSPG2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant has been reported to the ClinVar database as Uncertain Significance. The p.Arg2481Trp variant is novel (not in any individuals) in 1000 Genomes and allele frequency of 0.06034% is reported in gnomAD. The amino acid Arg at position 2481 is changed to a Trp changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by SIFT and the residue is conserved across species. The amino acid change p.Arg2481Trp in HSPG2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance .