NM_024675.4(PALB2):c.1450_1453dup (p.Thr485fs) AND Familial cancer of breast

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 28, 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:: RCV003501967.1

Allele description [Variation Report for NM_024675.4(PALB2):c.1450_1453dup (p.Thr485fs)]

NM_024675.4(PALB2):c.1450_1453dup (p.Thr485fs)

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.1450_1453dup (p.Thr485fs)

HGVS:

NC_000016.10:g.23635094_23635097dup
NG_007406.1:g.11262_11265dup
NM_001407296.1:c.1390_1393dup
NM_001407297.1:c.1450_1453dup
NM_001407298.1:c.1450_1453dup
NM_001407299.1:c.1450_1453dup
NM_001407300.1:c.1450_1453dup
NM_001407301.1:c.1450_1453dup
NM_001407302.1:c.1450_1453dup
NM_001407304.1:c.565_568dup
NM_001407305.1:c.565_568dup
NM_001407306.1:c.565_568dup
NM_001407307.1:c.565_568dup
NM_001407308.1:c.565_568dup
NM_001407309.1:c.565_568dup
NM_001407310.1:c.565_568dup
NM_001407311.1:c.565_568dup
NM_001407312.1:c.-104-4627_-104-4624dup
NM_001407313.1:c.-104-4627_-104-4624dup
NM_001407314.1:c.49-5821_49-5818dup
NM_024675.4:c.1450_1453dupMANE SELECT
NP_001394225.1:p.Thr465fs
NP_001394226.1:p.Thr485fs
NP_001394227.1:p.Thr485fs
NP_001394228.1:p.Thr485fs
NP_001394229.1:p.Thr485fs
NP_001394230.1:p.Thr485fs
NP_001394231.1:p.Thr485fs
NP_001394233.1:p.Thr190fs
NP_001394234.1:p.Thr190fs
NP_001394235.1:p.Thr190fs
NP_001394236.1:p.Thr190fs
NP_001394237.1:p.Thr190fs
NP_001394238.1:p.Thr190fs
NP_001394239.1:p.Thr190fs
NP_001394240.1:p.Thr190fs
NP_078951.2:p.Thr485Ilefs
NP_078951.2:p.Thr485fs
LRG_308t1:c.1449_1452dup
LRG_308:g.11262_11265dup
LRG_308p1:p.Thr485Ilefs
NC_000016.9:g.23646413_23646414insTTAA
NC_000016.9:g.23646415_23646418dup
NM_024675.3:c.1449_1452dup

Protein change:

T190fs

Molecular consequence:

NM_001407296.1:c.1390_1393dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407297.1:c.1450_1453dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407298.1:c.1450_1453dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407299.1:c.1450_1453dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407300.1:c.1450_1453dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407301.1:c.1450_1453dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407302.1:c.1450_1453dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407304.1:c.565_568dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407305.1:c.565_568dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407306.1:c.565_568dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407307.1:c.565_568dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407308.1:c.565_568dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407309.1:c.565_568dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407310.1:c.565_568dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407311.1:c.565_568dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024675.4:c.1450_1453dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407312.1:c.-104-4627_-104-4624dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001407313.1:c.-104-4627_-104-4624dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001407314.1:c.49-5821_49-5818dup - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial
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
SCV004311662	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 28, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17200668, 17200671, 17200672, 24136930, 25099575, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004311662

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 28, 2023)

germline

clinical testing

PubMed (6)
[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 (6)

Details of each submission

From Invitae, SCV004311662.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Thr485Ilefs*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 (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. 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: Feb 20, 2024

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