Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000206796 | SCV000260880 | likely benign | Ataxia-telangiectasia syndrome | 2024-01-09 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001355666 | SCV000512166 | likely benign | not provided | 2019-07-11 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000565986 | SCV000660475 | likely benign | Hereditary cancer-predisposing syndrome | 2014-11-24 | 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. |
Color Diagnostics, |
RCV000565986 | SCV000682235 | likely benign | Hereditary cancer-predisposing syndrome | 2016-11-17 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000206796 | SCV001260623 | uncertain significance | Ataxia-telangiectasia syndrome | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Sema4, |
RCV000565986 | SCV002527778 | likely benign | Hereditary cancer-predisposing syndrome | 2021-01-26 | criteria provided, single submitter | curation | |
Ce |
RCV001355666 | SCV004133258 | likely benign | not provided | 2022-06-01 | criteria provided, single submitter | clinical testing | ATM: BP4, BP7 |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001355666 | SCV004221138 | likely benign | not provided | 2023-02-23 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV003491959 | SCV004239283 | likely benign | Breast and/or ovarian cancer | 2022-10-19 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV004589891 | SCV005084086 | benign | Familial cancer of breast | 2024-05-21 | criteria provided, single submitter | clinical testing | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. |
Department of Pathology and Laboratory Medicine, |
RCV001355666 | SCV001550616 | likely benign | not provided | no assertion criteria provided | clinical testing | The ATM p.Leu1668= variant was not identified in the literature nor was it identified in the GeneInsight-COGR, Cosmic, MutDB, or LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs747317946) as “With Likely benign allele”, in ClinVar (as likely benign by Invitae, GeneDx, Ambry Genetics, and Color Genomics). The variant was identified in control databases in 5 of 245428 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include European (Non-Finnish) in 1 of 111058 chromosomes (freq: 0.000009), and Ashkenazi Jewish in 4 of 9832 chromosomes (freq: 0.000407), while the variant was not observed in the African, Other, Latino, East Asian, Finnish, and South Asian populations. The p.Leu1668= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. |