Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000486630 | SCV000571429 | uncertain significance | not provided | 2016-08-22 | criteria provided, single submitter | clinical testing | This in-frame duplication of 3 nucleotides in PALB2 is denoted c.1757_1759dupATG at the cDNA level and p.Asp586dup (D586dup) at the protein level. The normal sequence, with the bases that are duplicated in braces, is GATG[ATG]CTTT. This duplication of a single Aspartic Acid residue occurs at a position that is not conserved and is not located in a known functional domain (UniProt). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Since in-frame duplications may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider PALB2 Asp586dup to be a variant of uncertain significance. |
Ambry Genetics | RCV000564754 | SCV000665164 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-08 | criteria provided, single submitter | clinical testing | The c.1757_1759dupATG variant (also known as p.D586dup), located in coding exon 5 of the PALB2 gene, results from an in-frame duplication of ATG at nucleotide positions 1757 to 1759. This results in the duplication of an extra residue between codons 586 and 587. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be inconclusive by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001245580 | SCV001418877 | uncertain significance | Familial cancer of breast | 2021-12-02 | criteria provided, single submitter | clinical testing | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 403713). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.1757_1759dup, results in the insertion of 1 amino acid(s) of the PALB2 protein (p.Asp586dup), but otherwise preserves the integrity of the reading frame. |
Color Diagnostics, |
RCV000564754 | SCV004357901 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-31 | criteria provided, single submitter | clinical testing | This variant causes the duplication of 3 basepairs resulting in the in-frame duplication of Aspartic acid 586 in the PALB2 protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with ovarian cancer (ClinVar variation ID: 403713). This variant has not been identified 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. |
MVZ Praenatalmedizin und Genetik Nuernberg | RCV000474774 | SCV000503048 | uncertain significance | Neoplasm of ovary | 2017-02-28 | no assertion criteria provided | clinical testing | This rare variant (no ExAC-entry) of uncertain significance leads to an elongation of a short repeat of aspartic acids which show no significant conservation. In silico analyses show contradictory results. |