ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.62T>G (p.Leu21Ter)

gnomAD frequency: 0.00001  dbSNP: rs769240800
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507280 SCV000601794 pathogenic not provided 2020-03-15 criteria provided, single submitter clinical testing The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and found in general population data at a frequency that is consistent with pathogenicity.
Invitae RCV000535566 SCV000633465 pathogenic Familial cancer of breast 2024-01-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu21*) 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 (rs769240800, gnomAD 0.006%). 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: 439237). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000575810 SCV000666926 pathogenic Hereditary cancer-predisposing syndrome 2022-03-08 criteria provided, single submitter clinical testing The p.L21* pathogenic mutation (also known as c.62T>G), located in coding exon 2 of the PALB2 gene, results from a T to G substitution at nucleotide position 62. This changes the amino acid from a leucine to a stop codon within coding exon 2. 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.
GeneDx RCV000507280 SCV000680908 pathogenic not provided 2023-04-21 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32581362, 30799775, 17200668, 17200671, 17200672, 24136930, 25099575, 29922827, 29909963)
Academic Department of Medical Genetics, University of Cambridge RCV000575810 SCV000992221 pathogenic Hereditary cancer-predisposing syndrome 2018-01-26 criteria provided, single submitter research Application of AMCG guidelines 2015. Used other ClinVar submission evidence where relevant. Loss of heterozygosity in tumours or immunohistochemistry abnormalities considered functional evidence of pathogenicity.
Color Diagnostics, LLC DBA Color Health RCV000575810 SCV001354811 pathogenic Hereditary cancer-predisposing syndrome 2021-10-12 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 2 of the PALB2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in one individual affected with breast cancer in the literature (PMID: 29909963). This variant has been identified in 2/251470 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of PALB2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Sema4, Sema4 RCV000575810 SCV002531207 pathogenic Hereditary cancer-predisposing syndrome 2021-08-10 criteria provided, single submitter curation
Myriad Genetics, Inc. RCV000535566 SCV004189378 pathogenic Familial cancer of breast 2023-09-05 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Baylor Genetics RCV000535566 SCV004202629 pathogenic Familial cancer of breast 2023-05-22 criteria provided, single submitter clinical testing

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