ClinVar Miner

Submissions for variant NM_004260.3(RECQL4):c.3072_3073del (p.Val1026fs) (rs771538008)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000599050 SCV000710065 pathogenic not provided 2017-12-11 criteria provided, single submitter clinical testing The c.3072_3073delAG variant in the RECQL4 gene, reported as g.5446delAG using alternate nomenclature, has been reported previously in two unrelated individuals with Rothmund-Thomson syndrome who were heterozygous for c.3072_3073delAG and another protein truncating variant (Wang et al., 2003). One of these individuals had a diagnosis of osteosarcoma (Wang et al., 2003). The c.3072_3073delAG variant causes a frameshift starting with codon Valine 1026, changes this amino acid to an Alanine residue, and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Val1026AlafsX6. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.3072_3073delAG variant is observed in 3/15168 (0.02%) alleles from individuals of African background and 10/245054 (0.004%) total alleles in large population cohorts (Lek et al., 2016). We interpret c.3072_3073delAG as a pathogenic variant.
Invitae RCV000227479 SCV000288253 pathogenic Baller-Gerold syndrome 2018-09-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val1026Alafs*6) in the RECQL4 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs771538008, ExAC 0.03%). This variant has been observed as homozygous or compound heterozygous in individuals affected with Rothmund-Thomson syndrome (PMID: 18716613, 27247962). ClinVar contains an entry for this variant (Variation ID: 239754). Loss-of-function variants in RECQL4 are known to be pathogenic (PMID: 12734318, 12952869). For these reasons, this variant has been classified as Pathogenic.

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