ClinVar Miner

Submissions for variant NM_004260.3(RECQL4):c.1390+2del (rs386833843)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000812127 SCV000952431 pathogenic Baller-Gerold syndrome 2019-12-12 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 7 of the RECQL4 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs386833843, ExAC 0.5%). This variant has been observed as homozygous and compound heterozygous in several families affected with RAPADILINO syndrome and is considered to be a founder mutation in the Finnish population (PMID: 12952869, 18716613). This variant is also known as IVS7+2delT in the literature. ClinVar contains an entry for this variant (Variation ID: 56398). Experimental studies have shown that this variant results in exon 7 skipping and an in-frame deletion of 44 amino acids (PMID: 12952869, 22885111). This mutated protein shows loss of nuclear localization and impaired helicase and ATPase activity (PMID: 17250975, 22885111). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in RECQL4 are known to be pathogenic (PMID: 12734318, 12952869). For these reasons, this variant has been classified as Pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049811 SCV000082220 pathogenic Rapadilino syndrome no assertion criteria provided not provided Converted during submission to Pathogenic.

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