ClinVar Miner

Submissions for variant NM_181458.4(PAX3):c.86-2A>C

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV004788651 SCV005399683 likely pathogenic Waardenburg syndrome type 1 2024-10-09 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 Waardenburg syndrome type 1 (MIM#193500), Waardenburg syndrome type 3 (MIM#148820) and craniofacial-deafness-hand syndrome (MIM#122880). (I) 0108 - This gene is associated with both recessive and dominant disease. Waardenburg syndrome is typically dominant; however, recessive inheritance has been observed in more severe cases (PMID: 30854529). (I) 0115 - Variants in this gene are known to have variable expressivity (PMID: 20301703). (I) 0211 - Canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0704 - Another splice site variant comparable to the one identified in this case has limited previous evidence for pathogenicity. c.86-2A>G has been reported twice in ClinVar, once as likely pathogenic and once as pathogenic. This variant has also been reported in the literature in a family with Waardenburg syndrome type 1 (PMID:9232624). (SP) 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) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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