ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.5238+6G>A

gnomAD frequency: 0.00007  dbSNP: rs769544580
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001170112 SCV001332651 benign Familial thoracic aortic aneurysm and aortic dissection 2018-01-17 criteria provided, single submitter clinical testing
Invitae RCV001446488 SCV001649535 likely benign Aortic aneurysm, familial thoracic 7 2021-06-29 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001527010 SCV001737823 benign not specified 2021-05-24 criteria provided, single submitter clinical testing Variant summary: MYLK c.5238+6G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00016 in 251472 control chromosomes, predominantly at a frequency of 0.0011 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 22-fold the estimated maximal expected allele frequency for a pathogenic variant in MYLK causing Thoracic Aortic Aneurysms And Dissections phenotype (5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. To our knowledge, no occurrence of c.5238+6G>A in individuals affected with Thoracic Aortic Aneurysms And Dissections 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. Both laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx RCV000865600 SCV001796387 likely benign not provided 2021-01-11 criteria provided, single submitter clinical testing

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