ClinVar Miner

Submissions for variant NM_006265.3(RAD21):c.1183C>G (p.Pro395Ala)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center RCV004785165 SCV005397744 uncertain significance Cornelia de Lange syndrome 4 2024-02-06 criteria provided, single submitter clinical testing This sequence variant is a single nucleotide substitution (C>G) at position 1183 of the coding sequence of the RAD21 gene that results in a proline to alanine amino acid change at residue 395 of the RAD21 cohesin complex component protein. This residue falls in the STAG domain (PMID: 32687945), which plays a critical role in RAD21 cohesin complex component's chromosome maintenance and DNA repair functions. This variant is absent from ClinVar and the gnomAD v4.0.0 population database (0 of approximately 1,500,000 alleles). To our knowledge, this variant has not been observed in an individual affected by a RAD21-related disorder in the published literature. Multiple bioinformatic tools predict that this proline to alanine amino acid change would be damaging, and the Pro395 residue at this position is highly conserved across the vertebrate species examined. In addition, in silico splice predictors indicate that this nucleotide change may generate a novel splicing acceptor site. Studies examining the functional consequence of this variant have not been published, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this a variant of uncertain significance. ACMG Criteria: PM2, PP3

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