ClinVar Miner

Submissions for variant NM_152419.3(HGSNAT):c.852-2A>C (rs755710040)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000599289 SCV000710790 pathogenic not provided 2018-03-07 criteria provided, single submitter clinical testing The c.852-2A>C variant in the HGSNAT gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.852-2A>C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). This splice site variant destroys the canonical splice acceptor site in intron 9. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Additionally, a variant affecting the same canonincal splice site (c.852-1 G>A) has been previously reported as pathogenic in individuals with MPS IIIC (Stenson et al., 2014; Fedele et al.,2007). We interpret c.852-2A>C as a pathogenic variant.
Invitae RCV001041537 SCV001205158 pathogenic Mucopolysaccharidosis, MPS-III-C; Retinitis pigmentosa 73 2020-08-27 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 9 of the HGSNAT gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs755710040, ExAC 0.02%). Disruption of this splice site has been observed in several individuals affected with mucopolysaccharidosis type IIIC (MPS IIIC) and segregated with MPS IIIC in a family (PMID: 17397050). ClinVar contains an entry for this variant (Variation ID: 504466). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in HGSNAT are known to be pathogenic (PMID: 17033958, 19479962). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000669939 SCV000794740 likely pathogenic Mucopolysaccharidosis, MPS-III-C 2017-10-16 no assertion criteria provided clinical testing

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