ClinVar Miner

Submissions for variant NM_144670.6(A2ML1):c.3502+11C>T

gnomAD frequency: 0.00029  dbSNP: rs138636296
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001174886 SCV001338303 benign not specified 2020-02-14 criteria provided, single submitter clinical testing Variant summary: A2ML1 c.3502+11C>T 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 0.00029 in 248214 control chromosomes, predominantly at a frequency of 0.0041 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 1025 -fold the estimated maximal expected allele frequency for a pathogenic variant in A2ML1 causing Noonan Syndrome phenotype (4e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.3502+11C>T in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
GeneDx RCV001786448 SCV002028680 benign not provided 2021-11-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001786448 SCV002491677 benign not provided 2025-01-28 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV001786448 SCV005230529 benign not provided criteria provided, single submitter not provided

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