Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Preventiongenetics, |
RCV000709991 | SCV000810662 | pathogenic | Sandhoff disease | 2018-09-11 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000709991 | SCV000959270 | pathogenic | Sandhoff disease | 2023-03-15 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 256358). Disruption of this splice site has been observed in individual(s) with Sandhoff disease (PMID: 22848519, 31852446). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 2 of the HEXB gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in HEXB are known to be pathogenic (PMID: 7550345, 18758829). |
Foundation for Research in Genetics and Endocrinology, |
RCV000709991 | SCV001572886 | pathogenic | Sandhoff disease | 2021-02-12 | criteria provided, single submitter | clinical testing | A homozygous 3’ splice site variation in intron 2 of the HEXB gene was detected. The observed variant c.445+1G>C has not been reported in the 1000 genomes and ExAC databases. The in silico prediction of the variant is damaging by MutationTaster2. In summary, the variant meets our criteria to be classified as pathogenic. |