Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000666563 | SCV000790873 | likely pathogenic | Mucolipidosis type II; Pseudo-Hurler polydystrophy | 2017-04-12 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000666563 | SCV000893261 | pathogenic | Mucolipidosis type II; Pseudo-Hurler polydystrophy | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000666563 | SCV001398075 | pathogenic | Mucolipidosis type II; Pseudo-Hurler polydystrophy | 2023-08-28 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 13 of the GNPTAB 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 GNPTAB are known to be pathogenic (PMID: 19617216, 25107912). This variant is present in population databases (rs281865001, gnomAD 0.0009%). Disruption of this splice site has been observed in individuals with mucolipidosis or suspected mucolipidosis (PMID: 16116615, 21549105, 27662472, 29704188). ClinVar contains an entry for this variant (Variation ID: 39059). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV001588838 | SCV001827129 | pathogenic | not provided | 2019-10-03 | criteria provided, single submitter | clinical testing | Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 19617216, 29704188, 20301728, 25525159) |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001804753 | SCV002050961 | pathogenic | Mucolipidosis | 2021-12-02 | criteria provided, single submitter | clinical testing | Variant summary: GNPTAB c.2715+2T>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5` splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251262 control chromosomes (gnomAD). c.2715+2T>G has been reported in the literature in individuals affected with Mucolipidosis III (Cathey_2010, Oussoren_2018). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as pathogenic (n=2) and likely pathogenic (n=2). Based on the evidence outlined above, the variant was classified as pathogenic. |
Gene |
RCV000032324 | SCV000055969 | not provided | Pseudo-Hurler polydystrophy | no assertion provided | literature only |