Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV002051697 | SCV000271341 | pathogenic | Intellectual disability | 2015-07-15 | criteria provided, single submitter | clinical testing | The c.748+1G>T variant in CC2D1A has been reported in 2 Saudi Arabian families w ith spectrum of neurodevelopmental phenotypes, including nonsyndromic intellectu al disability, language impairment, autism spectrum disorder and seizures (Manzi ni 2014). The variant segregated with disease in a reccessive manner in a total of 11 individuals from both families and was absent from large population studie s. This variant occurs in the invariant region (+/- 1,2) of the splice consensus sequence and was shown to cause skipping of exon 6, resulting in complete loss of CC2D1A protein expression (Manzini 2014). In summary, this variant meets our criteria to be classified as pathogenic for nonsyndromic intellectual disability with or without seizures in an autosomal recessive manner (http://www.partners. org/personalizedmedicine/LMM) based upon segregation studies, absence from contr ols and functional studies. |
| Gene |
RCV000349177 | SCV000330343 | pathogenic | not provided | 2022-04-29 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease and demonstrated complete skipping of exon 6, leading to a premature stop codon (Manzini et al., 2014); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25066123, 28454995, 31130284, 32552793) |
| Baylor Genetics | RCV000985091 | SCV001524413 | pathogenic | Intellectual disability, autosomal recessive 3 | 2019-11-26 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Center for Genomic Medicine, |
RCV000985091 | SCV004806022 | pathogenic | Intellectual disability, autosomal recessive 3 | 2024-03-25 | criteria provided, single submitter | clinical testing | |
| Biochemical Molecular Genetic Laboratory, |
RCV000985091 | SCV001133053 | pathogenic | Intellectual disability, autosomal recessive 3 | 2019-09-26 | no assertion criteria provided | clinical testing | |
| Center for Genomic Medicine, |
RCV003989506 | SCV004806021 | uncertain significance | Premature ovarian failure 19 | 2024-03-25 | flagged submission | clinical testing | |
| Centre for Addiction & Mental Health, |
RCV004698484 | SCV005200251 | likely pathogenic | Autism | no assertion criteria provided | research | Putative loss-of-function variant, biallelic, in known disease gene; effect of canonical splice donor variant not yet validated |