Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001030366 | SCV000290862 | likely benign | Familial cancer of breast | 2023-01-12 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000575457 | SCV000674170 | likely benign | Hereditary cancer-predisposing syndrome | 2016-12-14 | 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, |
RCV000575457 | SCV000686000 | likely benign | Hereditary cancer-predisposing syndrome | 2017-05-01 | criteria provided, single submitter | clinical testing | |
| Leiden Open Variation Database | RCV001030366 | SCV001193327 | likely benign | Familial cancer of breast | 2019-05-13 | no assertion criteria provided | curation | Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitters to LOVD: Marc Tischkowitz, Yukihide Momozawa. |
| Department of Pathology and Laboratory Medicine, |
RCV001355003 | SCV001549755 | likely benign | Malignant tumor of breast | no assertion criteria provided | clinical testing | The PALB2 p.Pro1008= variant was identified in 9 of 14234 proband chromosomes (frequency: 0.0006) from Italian families and Japanese women with breast cancer and was present in 15 of 11391 control chromosomes (frequency: 001) from healthy individuals (Papi 2010, Momozawa 2018). The variant was also identified in dbSNP (ID: rs180177130) as “With Likely benign allele”, ClinVar (4x as likely benign by Invitae, Ambry Genetics, Color, PALB2 database), LOVD 3.0 (4x as benign). The variant was identified in control databases in 1 of 246232 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: East Asian in 1 of 17248 chromosomes (freq: 0.00006), while the variant was not observed in the African, Other, Latino, European Non-Finnish, Ashkenazi Jewish, European Finnish or South Asian populations. The p.Pro1008= 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) 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. |