ClinVar Miner

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

gnomAD frequency: 0.00005  dbSNP: rs541042265
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
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.
Fulgent Genetics, Fulgent Genetics RCV000763603 SCV000894448 likely pathogenic Microcephaly 1, primary, autosomal recessive 2022-05-18 criteria provided, single submitter clinical testing
Invitae RCV000483067 SCV003511810 uncertain significance not provided 2022-10-08 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 10 of the MCPH1 gene. However, it is currently unclear if variants that occur in this region of the gene cause disease. This variant is present in population databases (rs541042265, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with MCPH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 420681). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.