ClinVar Miner

Submissions for variant NM_024675.3(PALB2):c.2507_2509del (p.Val836del) (rs587782697)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132137 SCV000187208 uncertain significance Hereditary cancer-predisposing syndrome 2016-12-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000656935 SCV000292658 uncertain significance not provided 2018-12-03 criteria provided, single submitter clinical testing This deletion of three nucleotides in PALB2 is denoted c.2507_2509delTCG at the cDNA level and p.Val836del at the protein level. The normal sequence, with the bases that are deleted in brackets, is TCCG[delTCG]AACA. This in frame deletion of a single Valine residue is located in the region required for interaction with POLH and POLH DNA synthesis stimulation, as well as the region of interaction with BRCA2 (Oliver 2009, Buisson 2014). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. PALB2 Val836del was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Since in frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider PALB2 Val836del to be a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000354505 SCV000396092 uncertain significance Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000132137 SCV000396093 uncertain significance Hereditary cancer-predisposing syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000465007 SCV000550625 uncertain significance Familial cancer of breast 2018-09-05 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 5 of the PALB2 mRNA (c.2507_2509delTCG). This leads to the deletion of 1 amino acid residue in the PALB2 protein (p.Val836del) but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs587782697, ExAC 0.002%). This variant has not been reported in the literature in individuals with a PALB2-related disease. ClinVar contains an entry for this variant (Variation ID: 142756). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. In summary, this variant has uncertain impact on PALB2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000235515 SCV000601763 uncertain significance not specified 2016-08-17 criteria provided, single submitter clinical testing
Counsyl RCV000465007 SCV000784949 uncertain significance Familial cancer of breast 2017-02-16 criteria provided, single submitter clinical testing
Color RCV000132137 SCV000903544 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-17 criteria provided, single submitter clinical testing

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