Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000536634 | SCV000626354 | uncertain significance | Fanconi anemia | 2023-12-08 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 556 of the FANCM protein (p.Asp556Gly). This variant is present in population databases (rs148810507, gnomAD 0.04%). This missense change has been observed in individual(s) with personal and/or family history of breast cancer (PMID: 34326862, 34646395). ClinVar contains an entry for this variant (Variation ID: 456254). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Baylor Genetics | RCV001293939 | SCV001482641 | uncertain significance | Spermatogenic failure 28 | 2020-02-23 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Gene |
RCV001584242 | SCV001818811 | uncertain significance | not provided | 2025-01-21 | criteria provided, single submitter | clinical testing | Observed in individuals with a personal and/or family history of breast, ovarian, or other cancers, but also seen in unaffected controls (PMID: 28717660, 28881617, 34646395, 34326862, 33471991); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28717660, 28881617, 34646395, 34326862, 36848605, 33471991) |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001584242 | SCV002047108 | uncertain significance | not provided | 2024-02-01 | criteria provided, single submitter | clinical testing | The FANCM c.1667A>G (p.Asp556Gly) variant has been reported in the published literature in individuals with breast cancer (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/FANCM), 28717660 (2017)) and unspecified cancers (PMID: 34646395 (2021), 34326862 (2021)). This variant has also been identified in reportedly healthy individuals ((PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/FANCM)). The frequency of this variant in the general population, 0.00037 (13/35436 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Sema4, |
RCV002255431 | SCV002527316 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-23 | criteria provided, single submitter | curation | |
| Mendelics | RCV003492091 | SCV004232591 | likely benign | Hereditary cancer | 2024-01-23 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV005010491 | SCV005629819 | uncertain significance | Spermatogenic failure 28; Premature ovarian failure 15 | 2024-05-25 | criteria provided, single submitter | clinical testing |