Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000130541 | SCV000185410 | benign | Hereditary cancer-predisposing syndrome | 2014-12-01 | criteria provided, single submitter | clinical testing | General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance |
Labcorp Genetics |
RCV001084162 | SCV000252679 | benign | Neurofibromatosis, type 1 | 2025-02-02 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000217841 | SCV000269451 | benign | not specified | 2014-11-24 | criteria provided, single submitter | clinical testing | Cys851Cys in exon 21 of NF1: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 0.7% (33/4406) of Afr ican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2230852). |
Gene |
RCV000680357 | SCV000529105 | likely benign | not provided | 2021-02-05 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000217841 | SCV000595971 | likely benign | not specified | 2016-07-26 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000217841 | SCV000919884 | benign | not specified | 2018-08-13 | criteria provided, single submitter | clinical testing | Variant summary: NF1 c.2553C>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 0.00053 in 276370 control chromosomes, predominantly within the African subpopulation at a frequency of 0.0054 in the gnomAD database, including 1 homozygote. The observed variant frequency within African control individuals in the gnomAD database is approximately 26 fold of the estimated maximal expected allele frequency for a pathogenic variant in NF1 causing Neurofibromatosis Type 1 phenotype (0.00021), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. However, the region is highly homologous to pseudogenes, and the technology utilized for this dataset does not rule out pseudogene interference making ExAC and gnomAD data unreliable for assessing variant frequency. To our knowledge, no occurrence of c.2553C>T in individuals affected with Neurofibromatosis Type 1 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. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as Benign. |
Genome Diagnostics Laboratory, |
RCV001084162 | SCV001478988 | benign | Neurofibromatosis, type 1 | 2020-10-26 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000130541 | SCV002527464 | benign | Hereditary cancer-predisposing syndrome | 2020-09-19 | criteria provided, single submitter | curation | |
Genome- |
RCV001084162 | SCV002560211 | benign | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Institute for Biomarker Research, |
RCV000130541 | SCV004228009 | benign | Hereditary cancer-predisposing syndrome | 2023-11-06 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000680357 | SCV005436041 | likely benign | not provided | 2024-10-01 | criteria provided, single submitter | clinical testing | NF1: BP4, BP7 |