ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.788A>G (p.Glu263Gly)

gnomAD frequency: 0.00003  dbSNP: rs745553724
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164996 SCV000215690 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-26 criteria provided, single submitter clinical testing The p.E263G variant (also known as c.788A>G), located in coding exon 4 of the PALB2 gene, results from an A to G substitution at nucleotide position 788. The glutamic acid at codon 263 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and glycine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000233981 SCV000290888 uncertain significance Familial cancer of breast 2022-10-05 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 263 of the PALB2 protein (p.Glu263Gly). This variant is present in population databases (rs745553724, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 185553). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx RCV000485489 SCV000568111 uncertain significance not provided 2021-07-19 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 19369211, 27535533)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000485489 SCV001134558 uncertain significance not provided 2023-02-06 criteria provided, single submitter clinical testing The variant has not been reported in the published literature. The frequency of this variant in the general population, 0.0002 (7/34592 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Color Diagnostics, LLC DBA Color Health RCV000164996 SCV001356268 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-13 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with glycine at codon 263 of the PALB2 protein. Computational prediction suggests that this variant may not impact protein function. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 7/251416 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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.
Baylor Genetics RCV000233981 SCV004202067 uncertain significance Familial cancer of breast 2023-09-28 criteria provided, single submitter clinical testing

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