Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164268 | SCV000214893 | likely benign | Hereditary cancer-predisposing syndrome | 2015-01-21 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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. |
| Invitae | RCV000228877 | SCV000289673 | likely benign | Familial cancer of breast | 2023-12-27 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000164268 | SCV000684613 | likely benign | Hereditary cancer-predisposing syndrome | 2015-10-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001284480 | SCV000714640 | likely benign | not provided | 2019-12-05 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000228877 | SCV000786067 | likely benign | Familial cancer of breast | 2018-02-15 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001284480 | SCV001470307 | likely benign | not provided | 2020-01-21 | criteria provided, single submitter | clinical testing | |
| Myriad Genetics, |
RCV000228877 | SCV004020104 | benign | Familial cancer of breast | 2023-03-08 | 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, |
RCV001357970 | SCV001553585 | likely benign | Malignant tumor of breast | no assertion criteria provided | clinical testing | The CHEK2 p.Ala530= variant was not identified in the literature nor was it identified in Cosmic or Zhejiang University Database. The variant was identified in dbSNP (ID: rs786201796 as "With Likely benign, Uncertain significance allele") and ClinVar (classified as likely benign by Ambry Genetics, Invitae, Color Genomics, GeneDx, and Counsyl). The variant was identified in control databases in 4 of 260074 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 3 of 121966 chromosomes (freq: 0.00003), and South Asian in 1 of 30508 chromosomes (freq: 0.00003); it was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, and Finnish, populations. The p.Ala530= 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, 4 of 4 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. |