Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004788302 | SCV005399516 | pathogenic | Intellectual disability, X-linked 99, syndromic, female-restricted | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with X-linked intellectual disability 99 (MIM#300919) and X-linked syndromic intellectual disability 99 (MIM#300968). (I) 0108 - This gene is associated with both X-linked recessive and X-linked dominant disease. Partial loss of function missense variants result in X-linked recessive disease, predominantly affecting males. Variants resulting in a premature termination codon or a more complete loss of function are restricted to females in an X-linked dominant pattern of inheritance (PMID:31443933, PMID:26833328). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other premature termination variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Many NMD-predicted variants have been reported in females with intellectual disability/developmental delay and multiple congenital malformations (PMID: 26833328), and as likely pathogenic/pathogenic (ClinVar and DECIPHER). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1101 - Very strong and specific phenotype match for this individual. (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |