Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004790102 | SCV005400052 | likely pathogenic | Stickler syndrome type 2 | 2022-06-24 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with COL11A1-related skeletal dysplasias and deafness 37 (MIM#618533). Dominant negative is also a suggested mechanism (OMIM). (I) 0108 - This gene is associated with both recessive and dominant disease. Both missense variants and those predicted to result in a truncated protein, have been reported to cause recessive and dominant modes of disease. Marshall syndrome and Stickler syndrome have been reported with both dominant and recessive modes of inheritance (PMID: 32578940, PMID: 25073711), where the latter is usually caused by variants within exon 9. (I) 0115 - Variants in this gene causing Stickler syndrome are known to have variable expressivity (PMID: 27081569). (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to glutamic acid. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0601 - Variant is located in the well-established functional triple helical region. This variant disrupts a glycine within a G-X-Y repeat motif (PMID: 27081569, DECIPHER). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 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) 1207 - Parental origin of the variant is unresolved (by segregation analysis). Subsequent segregation showed this variant is not maternally inherited, however the father was not tested. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |