Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
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St. |
RCV003154595 | SCV003843113 | uncertain significance | Rothmund-Thomson syndrome type 2 | 2022-10-13 | criteria provided, single submitter | clinical testing | The RECQL4 c.2413_2421del (p.Ala805_Arg807del) change deletes nine nucleotides at position 2413-2421 resulting in an in-frame deletion of three amino acids in exon 15. This variant has been reported in trans with a loss-of-function variant (compound heterozygous) in multiple individuals with clinical features of Rothmund-Thomson syndrome (PMID: 31604778, internal data, personal communication). In addition, this variant has been reported as homozygous in an individual without obvious features of RECQL4-associated disorders (PMID: 31604778). This change has a maximum subpopulation frequency of 0.056% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as likely pathogenic depending on the zygosity of the variant. However, the currently available data suggest that this variant may only be associated with disease when detected in trans with a pathogenic variant (compound heterozygous), but not when detected in the homozygous state. |