NM_024675.4(PALB2):c.3432del (p.Gly1145fs) AND Familial cancer of breast

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 19, 2023
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:: RCV003501158.2

Allele description [Variation Report for NM_024675.4(PALB2):c.3432del (p.Gly1145fs)]

NM_024675.4(PALB2):c.3432del (p.Gly1145fs)

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.3432del (p.Gly1145fs)

HGVS:

NC_000016.10:g.23603588del
NG_007406.1:g.42770del
NM_001407296.1:c.3372del
NM_001407297.1:c.3360del
NM_001407298.1:c.3270del
NM_001407299.1:c.3195del
NM_001407300.1:c.3153del
NM_001407301.1:c.*67del
NM_001407302.1:c.*67del
NM_001407304.1:c.2547del
NM_001407305.1:c.2547del
NM_001407306.1:c.2547del
NM_001407307.1:c.2385del
NM_001407308.1:c.2310del
NM_001407309.1:c.2310del
NM_001407310.1:c.*67del
NM_001407311.1:c.*67del
NM_001407312.1:c.1644del
NM_001407313.1:c.*67del
NM_001407314.1:c.966del
NM_024675.4:c.3432delMANE SELECT
NP_001394225.1:p.Gly1125fs
NP_001394226.1:p.Gly1121fs
NP_001394227.1:p.Gly1091fs
NP_001394228.1:p.Gly1066fs
NP_001394229.1:p.Gly1052fs
NP_001394233.1:p.Gly850fs
NP_001394234.1:p.Gly850fs
NP_001394235.1:p.Gly850fs
NP_001394236.1:p.Gly796fs
NP_001394237.1:p.Gly771fs
NP_001394238.1:p.Gly771fs
NP_001394241.1:p.Gly549fs
NP_001394243.1:p.Gly323fs
NP_078951.2:p.Gly1145Valfs
NP_078951.2:p.Gly1145fs
LRG_308t1:c.3432del
LRG_308:g.42770del
LRG_308p1:p.Gly1145Valfs
NC_000016.9:g.23614909del
NM_024675.3:c.3432delC

Protein change:

G1052fs

Molecular consequence:

NM_001407301.1:c.*67del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001407302.1:c.*67del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001407310.1:c.*67del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001407311.1:c.*67del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001407313.1:c.*67del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001407296.1:c.3372del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407297.1:c.3360del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407298.1:c.3270del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407299.1:c.3195del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407300.1:c.3153del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407304.1:c.2547del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407305.1:c.2547del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407306.1:c.2547del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407307.1:c.2385del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407308.1:c.2310del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407309.1:c.2310del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407312.1:c.1644del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407314.1:c.966del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024675.4:c.3432del - 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
SCV004368057	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 19, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 17200668, 17200671, 19609323, 20927582, 21165770, 21365267, 22241545, 26315354, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004368057

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 19, 2023)

germline

clinical testing

PubMed (9)
[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 (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004368057.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This sequence change creates a premature translational stop signal (p.Gly1145Valfs*18) in the PALB2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the PALB2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. This variant disrupts a region of the PALB2 protein in which other variant(s) (p.Tyr1183*) have been determined to be pathogenic (PMID: 17200668, 17200671, 19609323, 20927582, 21165770, 21365267, 22241545, 26315354). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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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