NM_024675.4(PALB2):c.1976_1977del (p.Leu659fs) AND Familial cancer of breast

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 24, 2021
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:: RCV001942165.5

Allele description [Variation Report for NM_024675.4(PALB2):c.1976_1977del (p.Leu659fs)]

NM_024675.4(PALB2):c.1976_1977del (p.Leu659fs)

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.1976_1977del (p.Leu659fs)

HGVS:

NC_000016.10:g.23630177_23630178del
NG_007406.1:g.16180_16181del
NM_024675.4:c.1976_1977delMANE SELECT
NP_078951.2:p.Leu659fs
LRG_308t1:c.1976_1977del
LRG_308:g.16180_16181del
NC_000016.9:g.23641498_23641499del
NM_024675.3:c.1976_1977delTG

Protein change:

L659fs

Links:

dbSNP: rs2142384476

NCBI 1000 Genomes Browser:

rs2142384476

Molecular consequence:

NM_024675.4:c.1976_1977del - 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
SCV002235634	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 24, 2021)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 17200668, 17200671, 17200672, 24136930, 25099575, 31841383, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002235634

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 24, 2021)

germline

clinical testing

PubMed (7)
[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

Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer.

Reid S, Schindler D, Hanenberg H, Barker K, Hanks S, Kalb R, Neveling K, Kelly P, Seal S, Freund M, Wurm M, Batish SD, Lach FP, Yetgin S, Neitzel H, Ariffin H, Tischkowitz M, Mathew CG, Auerbach AD, Rahman N.

Nat Genet. 2007 Feb;39(2):162-4. Epub 2006 Dec 31.

PubMed [citation]

PMID:: 17200671

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002235634.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change creates a premature translational stop signal (p.Leu659Glnfs*3) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 17200671, 17200672, 24136930, 25099575). This variant is not present in population databases (ExAC no frequency). This premature translational stop signal has been observed in individual(s) with a personal or family history of breast and ovarian cancer (PMID: 31841383). For these reasons, this variant has been classified as Pathogenic.

#	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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