ClinVar Miner

Submissions for variant NM_005529.7(HSPG2):c.1355+5G>A

gnomAD frequency: 0.00001  dbSNP: rs781394836
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001812365 SCV001471605 uncertain significance not provided 2019-08-16 criteria provided, single submitter clinical testing The HSPG2 c.1355+5G>A variant (rs781394836), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is listed in the Genome Aggregation Database (gnomAD) with an overall population frequency of 0.0048 percent (identified on 12 out of 250,022 chromosomes). This is an intronic variant in a moderately conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by weakening the canonical donor site of intron 11. Altogether, there is not enough evidence to classify the c.1355+5G>A variant with certainty.
Labcorp Genetics (formerly Invitae), Labcorp RCV001812365 SCV002137517 uncertain significance not provided 2021-05-18 criteria provided, single submitter clinical testing This sequence change falls in intron 11 of the HSPG2 gene. It does not directly change the encoded amino acid sequence of the HSPG2 protein. It affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs781394836, ExAC 0.01%). This variant has not been reported in the literature in individuals with HSPG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 993585). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002276676 SCV002566743 uncertain significance Connective tissue disorder 2021-05-21 criteria provided, single submitter clinical testing

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