Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000671252 | SCV000796209 | likely pathogenic | Ceroid lipofuscinosis, neuronal, 6A | 2017-12-05 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002317912 | SCV000849928 | likely pathogenic | Inborn genetic diseases | 2016-11-02 | criteria provided, single submitter | clinical testing | The c.486+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 4 of the CLN6 gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6498 samples (12996 alleles) with coverage at this position. This nucleotide position is highly conserved in available vertebrate species. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
Invitae | RCV001868252 | SCV002256543 | likely pathogenic | Neuronal ceroid lipofuscinosis | 2023-11-01 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 4 of the CLN6 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 CLN6 are known to be pathogenic (PMID: 19135028). This variant is present in population databases (rs756522171, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with clinical features of neuronal ceroid lipofuscinosis (PMID: 12673792, 30561534). ClinVar contains an entry for this variant (Variation ID: 555430). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Fulgent Genetics, |
RCV002499177 | SCV002809798 | likely pathogenic | Ceroid lipofuscinosis, neuronal, 6A; Ceroid lipofuscinosis, neuronal, 6B (Kufs type) | 2021-09-07 | criteria provided, single submitter | clinical testing |