ClinVar Miner

Submissions for variant NM_024596.5(MCPH1):c.1480G>A (p.Ala494Thr)

gnomAD frequency: 0.00060  dbSNP: rs183880522
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000180367 SCV000232780 uncertain significance not provided 2014-06-11 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000180367 SCV001023093 benign not provided 2024-12-02 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001818445 SCV002066188 uncertain significance not specified 2019-01-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001818445 SCV004021210 likely benign not specified 2023-06-08 criteria provided, single submitter clinical testing Variant summary: MCPH1 c.1480G>A (p.Ala494Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00083 in 249454 control chromosomes, predominantly at a frequency of 0.0012 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is higher than the estimated maximal expected allele frequency for a pathogenic variant in MCPH1 causing Primary microcephaly phenotype (0.00091), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.1480G>A in individuals affected with Primary microcephaly and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.

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.