ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.3225T>A (p.Ser1075Arg)

gnomAD frequency: 0.00001  dbSNP: rs202222149
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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 RCV000218610 SCV000274441 likely benign Hereditary cancer-predisposing syndrome 2023-06-12 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV000466966 SCV000550711 uncertain significance Familial cancer of breast 2024-12-07 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 1075 of the PALB2 protein (p.Ser1075Arg). This variant is present in population databases (rs202222149, gnomAD 0.03%). This missense change has been observed in individual(s) with pancreatic cancer (PMID: 35171259). ClinVar contains an entry for this variant (Variation ID: 230775). 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. 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 RCV000218610 SCV000686016 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-21 criteria provided, single submitter clinical testing This missense variant replaces serine with arginine at codon 1075 of the PALB2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein structure and function. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been detected in a breast cancer case-control meta-analysis in 6/60466 cases and 8/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID PALB2_010768). This variant has been identified in 8/251470 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.
Sema4, Sema4 RCV000218610 SCV002530763 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-14 criteria provided, single submitter curation
Fulgent Genetics, Fulgent Genetics RCV002500726 SCV002812081 uncertain significance Familial cancer of breast; Fanconi anemia complementation group N; Pancreatic cancer, susceptibility to, 3 2021-07-06 criteria provided, single submitter clinical testing
Baylor Genetics RCV000466966 SCV004202611 uncertain significance Familial cancer of breast 2023-06-05 criteria provided, single submitter clinical testing

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