ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.2585del (p.Lys862fs)

dbSNP: rs752513498
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001390495 SCV001592235 pathogenic Familial cancer of breast 2024-04-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys862Argfs*9) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 17200671, 17200672, 24136930, 25099575). This variant is present in population databases (rs752513498, gnomAD 0.003%). 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: 1076548). For these reasons, this variant has been classified as Pathogenic.
GeneID Lab - Advanced Molecular Diagnostics RCV001775034 SCV002011814 likely pathogenic Hereditary cancer-predisposing syndrome 2018-10-10 criteria provided, single submitter clinical testing This variant results in an amino acid alteration, replacing a lysine (K) with an arginine (R) at position 862, creating a premature stop signal in the new reading frame (p.K862Rfs*9). The substitution is predicted to result in a non-functional PALB2 protein, either through protein truncation or nonsense-mediated mRNA decay. This variant is present in the gnomAD exomes database at a frequency of 0.00000398. Based on these findings and the limited literature regarding this substitution we consider it as a “likely pathogenic variant”.
Ambry Genetics RCV001775034 SCV004007909 pathogenic Hereditary cancer-predisposing syndrome 2023-05-01 criteria provided, single submitter clinical testing The c.2585delA pathogenic mutation, located in coding exon 6 of the PALB2 gene, results from a deletion of one nucleotide at nucleotide position 2585, causing a translational frameshift with a predicted alternate stop codon (p.K862Rfs*9). One study detected this mutation in 0/3030 pancreatic cancer cases and 1/123136 population controls (Hu C et al. JAMA, 2018 Jun;319:2401-2409). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV001390495 SCV004188493 pathogenic Familial cancer of breast 2023-09-13 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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