Submissions for variant NM_005529.7(HSPG2):c.10280G>A (p.Arg3427Gln)

gnomAD frequency: 0.00122  dbSNP: rs142939330

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000381320	SCV000354663	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	RCV000291620	SCV000354664	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.
Athena Diagnostics	RCV001283519	SCV000613688	benign	not specified	2020-07-30	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000974827	SCV001122695	likely benign	not provided	2023-12-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000974827	SCV001793637	likely benign	not provided	2018-11-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000974827	SCV003800050	uncertain significance	not provided	2022-04-08	criteria provided, single submitter	clinical testing	The HSPG2 c.10280G>A; p.Arg3427Gln variant (rs142939330), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 295739). This variant is found in the African population with an allele frequency of 0.21% (42/19,592 alleles) in the Genome Aggregation Database. The arginine at codon 3427 is weakly conserved, and computational analyses predict that this variant is neutral (REVEL: 0.021). Due to limited information, the clinical significance of the p.Arg3427Gln variant is uncertain at this time.
Revvity Omics, Revvity	RCV000974827	SCV003811338	uncertain significance	not provided	2019-10-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000974827	SCV005050649	likely benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	HSPG2: BP4
PreventionGenetics, part of Exact Sciences	RCV004543165	SCV004768089	likely benign	HSPG2-related disorder	2019-07-10	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).