ClinVar Miner

Submissions for variant NM_024675.3(PALB2):c.3116del (p.Asn1039fs) (rs180177133)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131150 SCV000186091 pathogenic Hereditary cancer-predisposing syndrome 2018-10-09 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000114595 SCV000260801 pathogenic Familial cancer of breast 2019-12-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn1039Ilefs*2) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Fanconi anemia, breast cancer, pancreatic cancer, and stomach cancer (PMID: 17200671, 17200668, 19264984, 20412113, 25452441, 26845104). ClinVar contains an entry for this variant (Variation ID: 126715). Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 24136930, 25099575). For these reasons, this variant has been classified as Pathogenic.
University of Washington Department of Laboratory Medicine, University of Washington RCV000131150 SCV000266106 pathogenic Hereditary cancer-predisposing syndrome 2015-11-20 criteria provided, single submitter clinical testing
Cancer Genetics Laboratory,Peter MacCallum Cancer Centre RCV000114595 SCV000267972 likely pathogenic Familial cancer of breast 2015-06-01 criteria provided, single submitter case-control
GeneDx RCV000235691 SCV000293156 pathogenic not provided 2017-12-29 criteria provided, single submitter clinical testing This deletion of one nucleotide in PALB2 is denoted c.3116delA at the cDNA level and p.Asn1039IlefsX2 (N1039IfsX2) at the protein level. The normal sequence, with the base that is deleted in brackets, is agGA[delA]TTTA, where the capital letters are exonic and lowercase letters are intronic. The deletion causes a frameshift, which changes an Asparagine to an Isoleucine at codon 1039, and creates a premature stop codon at position 2 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. PALB2 c.3116delA has been observed, in the compound heterozygous state, in an individual with Fanconi Anemia and a history of neuroblastoma and acute myeloid leukemia (Reid 2007). Additionally, this variant has been seen in association with familial breast and pancreatic cancer (Rahman 2007, Jones 2009, Slater 2010, Antoniou 2014, Thompson 2015). We consider this variant to be pathogenic.
Counsyl RCV000114595 SCV000488804 pathogenic Familial cancer of breast 2016-06-21 criteria provided, single submitter clinical testing
Color RCV000131150 SCV000690900 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Academic Department of Medical Genetics, University of Cambridge RCV000131150 SCV000992219 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.
OMIM RCV000114596 SCV000021458 pathogenic Fanconi anemia, complementation group N 2007-02-01 no assertion criteria provided literature only
OMIM RCV000001309 SCV000021459 risk factor Breast cancer, susceptibility to 2007-02-01 no assertion criteria provided literature only
OMIM RCV000114597 SCV000021463 risk factor Pancreatic cancer 3 2009-04-10 no assertion criteria provided literature only
Leiden Open Variation Database RCV000235691 SCV001193357 pathogenic not provided 2019-05-13 no assertion criteria provided curation Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitters to LOVD: Arleen D. Auerbach, LOVD-team, but with Curator vacancy, Marc Tischkowitz.

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