Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001525462 | SCV001735578 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-06-08 | criteria provided, single submitter | clinical testing | This variant causes a C to G nucleotide substitution at the -12 position of intron 13 of the CDH1 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251292 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV002070225 | SCV002332468 | likely benign | Hereditary diffuse gastric adenocarcinoma | 2023-12-04 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001355060 | SCV001549826 | uncertain significance | Malignant tumor of breast | no assertion criteria provided | clinical testing | The CDH1 c.2165-12C>G variant was not identified in the literature. The variant was identified in dbSNP (ID: rs760834250) “With Likely benign allele” and ClinVar (classified likely benign by GeneDx). The variant was identified in control databases in 1 of 246068 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017), observed in the South Asian population in 1 of 30782 chromosomes (freq: 0.00003), but not in the African, Other, Latino, European, Ashkenazi Jewish, East Asian, or Finnish populations. The c.2165-12C>G variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. In addition, 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predicts a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |