ClinVar Miner

Submissions for variant NM_000268.3(NF2):c.1386C>T (p.Arg462=) (rs138354622)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000562252 SCV000674136 likely benign Hereditary cancer-predisposing syndrome 2017-03-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
Athena Diagnostics Inc RCV000516813 SCV000614194 benign not specified 2016-12-30 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000516813 SCV000917899 benign not specified 2018-11-19 criteria provided, single submitter clinical testing Variant summary: NF2 c.1386C>T alters a non-conserved nucleotide resulting in a synonymous change. Several computational tools predict a significant impact on normal splicing: Five predict the variant creates a cryptic 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00034 in 210304 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.1386C>T in individuals affected with Neurofibromatosis Type 2 and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, 3 classified as likely benign/benign while one classified as VUS. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000473311 SCV000563474 benign Neurofibromatosis, type 2 2017-12-08 criteria provided, single submitter clinical testing
Mendelics RCV000473311 SCV000839522 uncertain significance Neurofibromatosis, type 2 2018-07-02 criteria provided, single submitter clinical testing

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