Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001080922 | SCV000284429 | benign | Neurofibromatosis, type 1 | 2024-01-27 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV000249416 | SCV000306253 | likely benign | not specified | criteria provided, single submitter | clinical testing | ||
Gene |
RCV000680361 | SCV000571396 | likely benign | not provided | 2017-10-02 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Sema4, |
RCV002257531 | SCV002527493 | likely benign | Hereditary cancer-predisposing syndrome | 2021-08-26 | criteria provided, single submitter | curation | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000249416 | SCV002555666 | benign | not specified | 2022-06-06 | criteria provided, single submitter | clinical testing | Variant summary: NF1 c.3197+9dupA alters a 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 0.00041 in 152128 control chromosomes (gnomAD v3.1, genomes dataset). However, the variant was found in the Amish subpopulation at a frequency of 0.044 (i.e. 40/912 alleles), including 2 homozygotes. This frequency is about 210-fold of the estimated maximum expected for a pathogenic variant in NF1 causing Neurofibromatosis Type 1 (0.001), suggesting that the variant is a benign polymorphism. c.3197+9dupA has been reported in the literature in individuals affected with various tumor phenotypes (examples: Schrader_2016, Henn_2019). However, in one of these reports a co-occurrence with another pathogenic variant has been reported (PTEN c.930_931delTA (p.Asp310Glufs*2) in Henn_2019), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has 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. |
Genome- |
RCV001080922 | SCV002560639 | likely benign | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004558584 | SCV005047821 | likely benign | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2015-05-22 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |