Submissions for variant NM_018451.5(CPAP):c.2872C>T (p.Arg958Ter)

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Total submissions: 3

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000497511	SCV000589826	likely pathogenic	not provided	2016-04-20	criteria provided, single submitter	clinical testing	The R958X variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R958X nonsense variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, it was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although this variant has not been reported previously to our knowledge, another truncating variant downstream of this position has been reported in the Human Gene Mutation Database in association with a CENPJ-related disorder (Stenson et al., 2014). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. GeneDx interprets R958X as a likely pathogenic variant.
Fulgent Genetics, Fulgent Genetics	RCV000762911	SCV000893323	pathogenic	Microcephaly 6, primary, autosomal recessive; Seckel syndrome 4	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000497511	SCV004651630	pathogenic	not provided	2023-05-13	criteria provided, single submitter	clinical testing	This variant is present in population databases (rs749343808, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg958*) in the CENPJ gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CENPJ are known to be pathogenic (PMID: 15793586, 16900296, 20522431). This variant has not been reported in the literature in individuals affected with CENPJ-related conditions. ClinVar contains an entry for this variant (Variation ID: 432139). For these reasons, this variant has been classified as Pathogenic.

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