CD164 was first reported in relation to autosomal dominant nonsyndromic hearing loss (AD NSHL) in 2015 (Nyegaard et al., PMID: 26197441). One pathogenic nonsense variant has been reported in 4 probands in 3 publications (PMIDs: 26197441, 35254497, 36454368). This variant was detected in families from different genetic ancestry groups which suggests that the Arg192 residue is a mutational hotspot, rather than a founder variant. This variant was found to segregate in 24 additional family members in two families (PMID: 26197441, 35254497). This gene disease relationship is also supported by expression and protein interaction studies (PMID: 26197441). In summary there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease association. This gene-disease pair was originally evaluated by the ClinGen Hearing Loss GCEP on 3/20/2018 as per SOP v6. It was reevaluated on 6/25/2024 using SOP v10. As a result of this reevaluation, new case level evidence has been reviewed or added, but the classification did not change (PMIDs: 35254497, 36454368, 36597107).
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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