NM_024675.3(PALB2):c.2515-1G>C AND Familial cancer of breast

Clinical significance:Likely pathogenic (Last evaluated: Sep 2, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000198016.3

Allele description [Variation Report for NM_024675.3(PALB2):c.2515-1G>C]

NM_024675.3(PALB2):c.2515-1G>C

Gene:
PALB2:partner and localizer of BRCA2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p12.2
Genomic location:
Preferred name:
NM_024675.3(PALB2):c.2515-1G>C
HGVS:
  • NC_000016.10:g.23629276C>G
  • NG_007406.1:g.17082G>C
  • NM_024675.3:c.2515-1G>C
  • LRG_308t1:c.2515-1G>C
  • LRG_308:g.17082G>C
  • NC_000016.9:g.23640597C>G
Links:
dbSNP: rs587776417
NCBI 1000 Genomes Browser:
rs587776417
Molecular consequence:
  • NM_024675.3:c.2515-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Familial cancer of breast
Synonyms:
Breast cancer, familial; CHEK2-Related Breast Cancer
Identifiers:
MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000253717Invitaecriteria provided, single submitter
Likely pathogenic
(Sep 2, 2020)
germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene.

Jones S, Hruban RH, Kamiyama M, Borges M, Zhang X, Parsons DW, Lin JC, Palmisano E, Brune K, Jaffee EM, Iacobuzio-Donahue CA, Maitra A, Parmigiani G, Kern SE, Velculescu VE, Kinzler KW, Vogelstein B, Eshleman JR, Goggins M, Klein AP.

Science. 2009 Apr 10;324(5924):217. doi: 10.1126/science.1171202. Epub 2009 Mar 5.

PubMed [citation]
PMID:
19264984
PMCID:
PMC2684332

Alternative splicing and ACMG-AMP-2015-based classification of PALB2 genetic variants: an ENIGMA report.

Lopez-Perolio I, Leman R, Behar R, Lattimore V, Pearson JF, Castéra L, Martins A, Vaur D, Goardon N, Davy G, Garre P, García-Barberán V, Llovet P, Pérez-Segura P, Díaz-Rubio E, Caldés T, Hruska KS, Hsuan V, Wu S, Pesaran T, Karam R, Vallon-Christersson J, et al.

J Med Genet. 2019 Jul;56(7):453-460. doi: 10.1136/jmedgenet-2018-105834. Epub 2019 Mar 19.

PubMed [citation]
PMID:
30890586
PMCID:
PMC6591742
See all PubMed Citations (8)

Details of each submission

From Invitae, SCV000253717.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This sequence change affects an acceptor splice site in intron 5 of the PALB2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs587776417, ExAC 0.009%). Disruption of this splice site has been observed in individual(s) with breast and pancreatic cancer (PMID: 19264984, 21285249). ClinVar contains an entry for this variant (Variation ID: 216006). Experimental studies have shown that disruption of this splice site disrupts mRNA splicing (PMID: 30890586,21285249). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 24136930, 25099575). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 10, 2021

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