ClinVar Miner

Submissions for variant NM_024596.5(MCPH1):c.1974-2A>G (rs541042265)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000763603 SCV000894448 likely pathogenic Primary autosomal recessive microcephaly 1 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000483067 SCV000569613 likely pathogenic not provided 2016-03-28 criteria provided, single submitter clinical testing A c.1974-2 A>G variant that is likely pathogenic has been identified in the MCPH1 gene. The c.1974-2 A>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. However, the 1000 Genomes Project reports this variant was observed in 2/186 (1%) alleles from individuals of Chinese background. The c.1974-2 A>G splice site variant in the MCPH1 gene destroys the canonical splice acceptor site in intron 10. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. However, in the absence of RNA/functional studies, the actual effect of this sequence change is unknown. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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