ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.2145+1G>C (rs1057520726)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000425852 SCV000517191 likely pathogenic not provided 2017-07-31 criteria provided, single submitter clinical testing The c.2145+1 G>C likely pathogenic variant in the PKP2 gene was initially reported in an individual with a clinicaldiagnosis of ARVC who presented with symptom onset at age 64; however, this individual also harbored a secondvariant in PKP2 (den Haan et al., 2009). Subsequently, Tan et al. (2010) identified c.2145+1 G>C in an individualwith late-onset ARVC, defined as symptom onset at or after age 50. Additionally, the c.2145+1 G>C variant was notobserved in approximately 6,500 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project, indicating it is not a common benign variant in these populations. This variant is predicted todestroy the splice donor site in intron 10 and lead to skipping of the adjacent exon 10. Moreover, other splice sitevariants in the PKP2 gene have been reported in the Human Gene Mutation Database in association with ARVD/C(Stenson et al., 2014). However, in the absence of functional mRNA studies, the physiological consequence of thisvariant cannot be precisely determined.Therefore, this variant is likely pathogenic. In order to definitively determine its clinical significance, additional datais required.

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