NM_024675.4(PALB2):c.2391del (p.Gln797fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 24, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000210140.6

Allele description [Variation Report for NM_024675.4(PALB2):c.2391del (p.Gln797fs)]

NM_024675.4(PALB2):c.2391del (p.Gln797fs)

Gene:

PALB2:partner and localizer of BRCA2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NM_024675.4(PALB2):c.2391del (p.Gln797fs)

Other names:

NM_024675.3:c.2391del

HGVS:

NC_000016.10:g.23629764del
NG_007406.1:g.16595del
NM_024675.4:c.2391delMANE SELECT
NP_078951.2:p.Gln797fs
LRG_308:g.16595del
NC_000016.9:g.23641084del
NC_000016.9:g.23641085del
NM_024675.3:c.2391delA

Protein change:

Q797fs

Links:

dbSNP: rs1555460360

NCBI 1000 Genomes Browser:

rs1555460360

Molecular consequence:

NM_024675.4:c.2391del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000266104	University of Washington Department of Laboratory Medicine, University of Washington	criteria provided, single submitter (Shirts et al. (Genet Med 2016))	Pathogenic (Nov 20, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002737112	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jan 24, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23824750, 26283626, 26786923 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000266104

University of Washington Department of Laboratory Medicine, University of Washington

criteria provided, single submitter

(Shirts et al. (Genet Med 2016))

Pathogenic
(Nov 20, 2015)

germline

clinical testing

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

SCV002737112

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jan 24, 2020)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Improving performance of multigene panels for genomic analysis of cancer predisposition.

Shirts BH, Casadei S, Jacobson AL, Lee MK, Gulsuner S, Bennett RL, Miller M, Hall SA, Hampel H, Hisama FM, Naylor LV, Goetsch C, Leppig K, Tait JF, Scroggins SM, Turner EH, Livingston R, Salipante SJ, King MC, Walsh T, Pritchard CC.

Genet Med. 2016 Oct;18(10):974-81. doi: 10.1038/gim.2015.212. Epub 2016 Feb 4.

PubMed [citation]

PMID:: 26845104

Low prevalence of germline PALB2 mutations in Australian triple-negative breast cancer.

Wong-Brown MW, Avery-Kiejda KA, Bowden NA, Scott RJ.

Int J Cancer. 2014 Jan 15;134(2):301-5. doi: 10.1002/ijc.28361. Epub 2013 Sep 23.

PubMed [citation]

PMID:: 23824750

See all PubMed Citations (4)

Details of each submission

From University of Washington Department of Laboratory Medicine, University of Washington, SCV000266104.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	1	not provided	not provided		1	not provided	not provided	not provided

From Ambry Genetics, SCV002737112.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The c.2391delA pathogenic mutation, located in coding exon 5 of the PALB2 gene, results from a deletion of one nucleotide at nucleotide position 2391, causing a translational frameshift with a predicted alternate stop codon (p.Q797Hfs*54). This mutation (designated as c.2390del) was detected in 1/347 Australian triple-negative breast cancer patients (Wong-Brown MW et al. Int. J. Cancer, 2014 Jan;134:301-5). It was also reported in a patient with breast cancer and a family history of melanoma, non-Hodgkin's lymphoma, bladder cancer, and breast cancer (Thompson ER et al. Breast Cancer Res., 2015 Aug;17:111). 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 8, 2024

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