ClinVar Miner

Submissions for variant NM_005236.2(ERCC4):c.2169C>A (p.Cys723Ter) (rs2020959)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000822020 SCV000962800 uncertain significance Xeroderma pigmentosum, group F; Cockayne syndrome; Fanconi anemia, complementation group Q 2019-07-26 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the ERCC4 gene (p.Cys723*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 194 amino acids of the ERCC4 protein. This variant is present in population databases (rs2020959, ExAC 0.06%). This variant has been observed in an individual affected with giant cell tumor of bone and in an individual affected with alveolar rhabdomyosarcoma (PMID: 28878254). Experimental studies have shown that this nonsense change attenuates DNA repair and stimulates proteosomal degradation (PMID: 24412486). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Leiden Open Variation Database RCV001194781 SCV001364567 uncertain significance not provided 2017-03-28 no assertion criteria provided curation Curator: Arleen D. Auerbach. Submitter to LOVD: Gerard C.P. Schaafsma.

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