NM_024675.4(PALB2):c.2959_2966dup (p.Glu990fs) AND Familial cancer of breast

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Apr 16, 2017)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000532289.2

Allele description [Variation Report for NM_024675.4(PALB2):c.2959_2966dup (p.Glu990fs)]

NM_024675.4(PALB2):c.2959_2966dup (p.Glu990fs)

Gene:
PALB2:partner and localizer of BRCA2 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
16p12.2
Genomic location:
Preferred name:
NM_024675.4(PALB2):c.2959_2966dup (p.Glu990fs)
HGVS:
  • NC_000016.10:g.23623000_23623007dup
  • NG_007406.1:g.23352_23359dup
  • NM_024675.4:c.2959_2966dupMANE SELECT
  • NP_078951.2:p.Glu990fs
  • LRG_308:g.23352_23359dup
  • NC_000016.9:g.23634321_23634328dup
  • NM_024675.3:c.2959_2966dupCAACAAGT
Protein change:
E990fs
Links:
dbSNP: rs875989792
NCBI 1000 Genomes Browser:
rs875989792
Molecular consequence:
  • NM_024675.4:c.2959_2966dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000267969Cancer Genetics Laboratory,Peter MacCallum Cancer Centrecriteria provided, single submitter
Likely pathogenic
(Jun 1, 2015)
germlinecase-control

PubMed (1)
[See all records that cite this PMID]

SCV000633393Invitaecriteria provided, single submitter
Pathogenic
(Apr 16, 2017)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineno1not providednot provided1998not providedcase-control

Citations

PubMed

Prevalence of PALB2 mutations in Australian familial breast cancer cases and controls.

Thompson ER, Gorringe KL, Rowley SM, Wong-Brown MW, McInerny S, Li N, Trainer AH, Devereux L, Doyle MA, Li J, Lupat R, Delatycki MB; LifePool Investigators., Mitchell G, James PA, Scott RJ, Campbell IG.

Breast Cancer Res. 2015 Aug 19;17:111. doi: 10.1186/s13058-015-0627-7.

PubMed [citation]
PMID:
26283626
PMCID:
PMC4539664

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Cancer Genetics Laboratory,Peter MacCallum Cancer Centre, SCV000267969.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedcase-control PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineno1998not providednot provided1not providednot providednot provided

From Invitae, SCV000633393.1

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

Description

This sequence change creates a premature translational stop signal at codon 990 (p.Glu990Asnfs*3) of the PALB2 gene. It is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature in an individual affected with a PALB2-related disease, loss-of-function variants in PALB2 are known to be pathogenic (PMID: 25099575, 17200668). This variant is also known as c.2966_2967insCAACAAGT in the literature. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 27, 2021

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