NM_024675.4(PALB2):c.1037_1038del (p.Lys346fs) AND Familial cancer of breast

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 20, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000814528.6

Allele description [Variation Report for NM_024675.4(PALB2):c.1037_1038del (p.Lys346fs)]

NM_024675.4(PALB2):c.1037_1038del (p.Lys346fs)

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.1037_1038del (p.Lys346fs)

HGVS:

NC_000016.10:g.23635510_23635511del
NC_000016.9:g.23646829_23646830del
NG_007406.1:g.10849_10850del
NM_024675.4:c.1037_1038delMANE SELECT
NP_078951.2:p.Lys346fs
LRG_308:g.10849_10850del
NC_000016.9:g.23646829_23646830del
NC_000016.9:g.23646829_23646830delTT
NC_000016.9:g.23646831_23646832del
NM_024675.3:c.1037_1038delAA

Protein change:

K346fs

Links:

dbSNP: rs1597097438

NCBI 1000 Genomes Browser:

rs1597097438

Molecular consequence:

NM_024675.4:c.1037_1038del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial; Hereditary breast cancer
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000954941	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 20, 2018)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17200668, 24136930, 25099575, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000954941

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 20, 2018)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene.

Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, Reid S, Spanova K, Barfoot R, Chagtai T, Jayatilake H, McGuffog L, Hanks S, Evans DG, Eccles D; Breast Cancer Susceptibility Collaboration (UK)., Easton DF, Stratton MR.

Nat Genet. 2007 Feb;39(2):165-7. Epub 2006 Dec 31.

PubMed [citation]

PMID:: 17200668
PMCID:: PMC2871593

The PALB2 gene is a strong candidate for clinical testing in BRCA1- and BRCA2-negative hereditary breast cancer.

Janatova M, Kleibl Z, Stribrna J, Panczak A, Vesela K, Zimovjanova M, Kleiblova P, Dundr P, Soukupova J, Pohlreich P.

Cancer Epidemiol Biomarkers Prev. 2013 Dec;22(12):2323-32. doi: 10.1158/1055-9965.EPI-13-0745-T. Epub 2013 Oct 17.

PubMed [citation]

PMID:: 24136930

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000954941.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 24136930, 25099575). This variant has not been reported in the literature in individuals with PALB2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Lys346Argfs*14) in the PALB2 gene. It is expected to result in an absent or disrupted protein product.

#	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 29, 2024

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