ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.3287A>G (p.Asn1096Ser)

dbSNP: rs786201142
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162754 SCV000213230 uncertain significance Hereditary cancer-predisposing syndrome 2020-12-08 criteria provided, single submitter clinical testing The p.N1096S variant (also known as c.3287A>G), located in coding exon 12 of the PALB2 gene, results from an A to G substitution at nucleotide position 3287. The asparagine at codon 1096 is replaced by serine, an amino acid with highly similar properties. This alteration was detected in a Portuguese high-risk breast cancer family but was not observed in a series of 311 additional Portuguese index cases (Hartley T, Hered Cancer Clin Pract 2014 ; 12(1):19). This amino acid position is highly 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.
Invitae RCV001030403 SCV001517383 uncertain significance Familial cancer of breast 2023-10-17 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1096 of the PALB2 protein (p.Asn1096Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 25225577, 30638972). ClinVar contains an entry for this variant (Variation ID: 183891). 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 disruptive. 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 RCV000162754 SCV004357812 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-06 criteria provided, single submitter clinical testing This missense variant replaces asparagine with serine at codon 1096 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 with bilateral breast cancer (PMID: 25225577). 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.
Leiden Open Variation Database RCV001030403 SCV001193381 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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