The COL11A2 gene has been reported in relationship with multiple conditions and inheritance patterns. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found differences in variant type, inheritance pattern, and phenotype within reported COL11A2 cases. Therefore we have split curations by inheritance pattern and again by nonsyndromic hearing loss and Stickler syndrome and assessed separately. This assessment focuses on its relationship to autosomal recessive nonsyndromic hearing loss. The COL11A2 gene was first associated with this disease in humans as early as 2005 (Chen et al.). At least 4 missense variants and 2 null variants in 5 probands have been reported in humans (PMIDs: 25633957, 16033917, MORL unpublished data). Variants in this gene segregated with disease in 10 additional family members. This gene-disease relationship is supported by relevant expression and functional studies. In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This gene-disease pair was originally evaluated by the Hearing Loss GCEP on 12/20/2018. It was re-evaluated on 11/15/2023. As a result of this reevaluation, the classification did not change. However additional genetic evidence (PMID: 33597575) and experimental evidence in the form of a mouse model (PMID:10581026) have been included with scoring adjusted to the current Gene Clinical Validity SOP Version 9.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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