ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1416C>T (p.Leu472=) (rs148776784)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000467708 SCV000563479 benign Neurofibromatosis, type 2 2020-12-07 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000517593 SCV000614195 benign not specified 2016-12-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV000568407 SCV000674137 likely benign Hereditary cancer-predisposing syndrome 2017-03-20 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000517593 SCV000917900 benign not specified 2018-11-19 criteria provided, single submitter clinical testing Variant summary: NF2 c.1416C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 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 0.0003 in 208386 control chromosomes, predominantly at a frequency of 0.0033 within the African subpopulation in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 174 fold of the estimated maximal expected allele frequency for a pathogenic variant in NF2 causing Neurofibromatosis Type 2 phenotype (1.9e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.1416C>T in individuals affected with Neurofibromatosis Type 2 and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.

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