Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV001255761 | SCV002766916 | pathogenic | Microcephaly and chorioretinopathy 1 | 2022-09-02 | 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 microcephaly and chorioretinopathy 1 (MIM#251270). (I) 0106 - This gene is associated with autosomal recessive disease. (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) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (7 heterozygotes, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. These variants have been reported many times as pathogenic (DECIPHER). (SP) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. This variant has been reported as likely pathogenic (ClinVar). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1207 - Parental origin of the variant is unresolved (by duo analysis). This variant was not maternally inherited. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Invitae | RCV002570594 | SCV002998133 | pathogenic | not provided | 2022-11-21 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 977849). This variant has not been reported in the literature in individuals affected with TUBGCP6-related conditions. This variant is present in population databases (rs770253928, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Trp539Glyfs*27) in the TUBGCP6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TUBGCP6 are known to be pathogenic (PMID: 25344692). |
| Service de Génétique Moléculaire, |
RCV001255761 | SCV001432358 | likely pathogenic | Microcephaly and chorioretinopathy 1 | no assertion criteria provided | clinical testing |