ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.560C>A (p.Pro187His)

gnomAD frequency: 0.00006  dbSNP: rs371582757
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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 RCV000563795 SCV000665072 likely benign Hereditary cancer-predisposing syndrome 2024-01-14 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.
Color Diagnostics, LLC DBA Color Health RCV000563795 SCV000686067 likely benign Hereditary cancer-predisposing syndrome 2021-05-19 criteria provided, single submitter clinical testing
Invitae RCV000635903 SCV000757329 likely benign Familial cancer of breast 2024-01-11 criteria provided, single submitter clinical testing
Mendelics RCV003492103 SCV001140053 likely benign Hereditary cancer 2024-01-23 criteria provided, single submitter clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000635903 SCV002512649 uncertain significance Familial cancer of breast 2021-11-22 criteria provided, single submitter clinical testing ACMG classification criteria: BP4 supporting
Quest Diagnostics Nichols Institute San Juan Capistrano RCV002476221 SCV002774676 uncertain significance not provided 2021-06-15 criteria provided, single submitter clinical testing
GeneDx RCV002476221 SCV003842547 uncertain significance not provided 2023-03-17 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with breast cancer or Fanconi anemia (George et al., 2021; Guindalini et al., 2022); This variant is associated with the following publications: (PMID: 20871615, 19369211, 35264596, 34585473, 30949167)
Neuberg Centre For Genomic Medicine, NCGM RCV003448324 SCV004176579 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 5 2023-02-14 criteria provided, single submitter clinical testing The missense c.560C>A (p.Pro187His) variant in PALB2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Pro187His variant has allele frequency 0.006% is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Likely benign / Uncertain Significance. The amino acid change p.Pro187His in PALB2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Pro at position 187 is changed to a His changing protein sequence and it might alter its composition and physico-chemical properties For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).

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