ClinVar Miner

Submissions for variant NM_001363118.2(SLC52A2):c.808C>T (p.Gln270Ter)

gnomAD frequency: 0.00003  dbSNP: rs375088539
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235507 SCV000292961 pathogenic not provided 2023-06-21 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 27148561, 34493867, 31836589, 30487145)
Labcorp Genetics (formerly Invitae), Labcorp RCV000167765 SCV000955813 pathogenic Brown-Vialetto-van Laere syndrome 2 2023-08-30 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 188051). This premature translational stop signal has been observed in individual(s) with Brown-Vialetto-Van Laere syndrome (BVVLS) (PMID: 27148561). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs375088539, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Gln270*) in the SLC52A2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC52A2 are known to be pathogenic (PMID: 24253200).
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002272152 SCV002557151 pathogenic Brown-Vialetto-van Laere syndrome 1 2022-09-02 criteria provided, single submitter clinical testing A heterozygous nonsense variant was identified, NM_001253816.1(SLC52A2):c.808C>T in exon 3 of 5 of the SLC52A2 gene. This nonsense variant is predicted to create a change of a glutamine to a stop at amino acid position 270 of the protein; NP_001240745.1(SLC52A2):p.(Gln270*), resulting in the loss of normal protein function through nonsense-mediated decay (NMD). The variant is present in the gnomAD population database at a global population frequency of 0.0014% (4 heterozygotes, 0 homozygotes) with an African sub-population frequency of 0.0040%. The variant has been previously reported in patients with Brown-Vialetto-Van Laere syndrome (ClinVar, LOVD, Petrovski, S. et al. (2015)). Other variants predicted to cause NMD have also been reported as pathogenic in individuals with this Brown-Vialetto-Van Laere syndrome (ClinVar, Foley, A. R. et al. (2014)). Based on information available at the time of curation, this variant has been classified as PATHOGENIC.
Duke University Health System Sequencing Clinic, Duke University Health System RCV000167765 SCV000218457 pathogenic Brown-Vialetto-van Laere syndrome 2 2015-03-25 no assertion criteria provided research

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