ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.3244A>G (p.Ser1082Gly)

gnomAD frequency: 0.00002  dbSNP: rs786203345
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166614 SCV000217418 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-03 criteria provided, single submitter clinical testing The p.S1082G variant (also known as c.3244A>G), located in coding exon 12 of the PALB2 gene, results from an A to G substitution at nucleotide position 3244. The serine at codon 1082 is replaced by glycine, an amino acid with similar properties. This alteration was detected on a 25-gene panel test in a woman who was diagnosed with breast cancer before age 50 (Tung N et al. Cancer, 2015 Jan;121:25-33). This amino acid position is not well conserved in available 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 RCV000232382 SCV000290870 uncertain significance Familial cancer of breast 2024-11-25 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 1082 of the PALB2 protein (p.Ser1082Gly). This variant is present in population databases (rs786203345, gnomAD 0.01%). 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: 186946). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (internal data). 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.
Color Diagnostics, LLC DBA Color Health RCV000166614 SCV000690908 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-26 criteria provided, single submitter clinical testing This missense variant replaces serine with glycine at codon 1082 of the PALB2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected breast cancer (PMID: 25186627). This variant has been identified in 5/251472 chromosomes 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.
Fulgent Genetics, Fulgent Genetics RCV002505212 SCV002815475 uncertain significance Familial cancer of breast; Fanconi anemia complementation group N; Pancreatic cancer, susceptibility to, 3 2021-12-10 criteria provided, single submitter clinical testing
Baylor Genetics RCV000232382 SCV004201998 uncertain significance Familial cancer of breast 2023-10-26 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV004998351 SCV005623223 uncertain significance not provided 2024-03-27 criteria provided, single submitter clinical testing The PALB2 c.3244A>G (p.Ser1082Gly) variant has been reported in the published literature in an individual with breast cancer (PMID: 25186627 (2015)) and in a reportedly healthy individual (PMID: 32906206 (2020), see also LOVD (http://databases.lovd.nl/shared)). The frequency of this variant in the general population, 0.00014 (5/34592 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the 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.
Leiden Open Variation Database RCV000232382 SCV001193374 uncertain significance Familial cancer of breast 2019-05-13 no assertion criteria provided curation Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Marc Tischkowitz.

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