Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001369696 | SCV001566143 | likely benign | not provided | 2022-10-13 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV004789551 | SCV005398158 | uncertain significance | 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 VUS-3B. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Stickler syndrome, type II (MIM#604841). 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 both recessive and dominant modes of disease. Marshall syndrome and Stickler syndrome have been reported with both dominant and recessive modes of inheritance (PMIDs: 32578940, 25073711), and 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 proline to histidine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v2) <0.001 for a dominant condition (3 heterozygotes, 0 homozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v3) (1 heterozygote, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated collagen repeat domain (DECIPHER). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. This variant has been classified as a VUS once by a clinical laboratory in ClinVar. (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) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |