Submissions for variant NM_005529.7(HSPG2):c.8961C>T (p.Gly2987=)

gnomAD frequency: 0.00028  dbSNP: rs369899077

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000370440	SCV000336963	uncertain significance	not provided	2015-11-09	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000277852	SCV000354715	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000297842	SCV000354716	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000370440	SCV000885594	uncertain significance	not provided	2017-10-23	criteria provided, single submitter	clinical testing
Invitae	RCV000370440	SCV001066956	likely benign	not provided	2023-11-24	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000370440	SCV003811918	uncertain significance	not provided	2020-07-08	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003401246	SCV004120079	uncertain significance	HSPG2-related condition	2023-06-13	criteria provided, single submitter	clinical testing	The HSPG2 c.8961C>T variant is not predicted to result in an amino acid change (p.=). This variant may enhance a cryptic splice site based on available splicing prediction programs (Alamut Visual Plus v1.6.1), however the use of computer prediction programs is not equivalent to functional evidence. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.042% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-22168823-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.