NM_024675.4(PALB2):c.3077dup (p.Leu1027fs) AND Familial cancer of breast

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 20, 2023
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:: RCV003501116.3

Allele description [Variation Report for NM_024675.4(PALB2):c.3077dup (p.Leu1027fs)]

NM_024675.4(PALB2):c.3077dup (p.Leu1027fs)

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.3077dup (p.Leu1027fs)

HGVS:

NC_000016.10:g.23621398dup
NG_007406.1:g.24960dup
NM_001407296.1:c.3017dup
NM_001407297.1:c.3005dup
NM_001407298.1:c.2915dup
NM_001407299.1:c.3077dup
NM_001407300.1:c.2834+2611dup
NM_001407301.1:c.3077dup
NM_001407302.1:c.2915dup
NM_001407304.1:c.2192dup
NM_001407305.1:c.2192dup
NM_001407306.1:c.2192dup
NM_001407307.1:c.2030dup
NM_001407308.1:c.2192dup
NM_001407309.1:c.2192dup
NM_001407310.1:c.2192dup
NM_001407311.1:c.2192dup
NM_001407312.1:c.1289dup
NM_001407313.1:c.1289dup
NM_001407314.1:c.611dup
NM_024675.4:c.3077dupMANE SELECT
NP_001394225.1:p.Leu1007fs
NP_001394226.1:p.Leu1003fs
NP_001394227.1:p.Leu973fs
NP_001394228.1:p.Leu1027fs
NP_001394230.1:p.Leu1027fs
NP_001394231.1:p.Leu973fs
NP_001394233.1:p.Leu732fs
NP_001394234.1:p.Leu732fs
NP_001394235.1:p.Leu732fs
NP_001394236.1:p.Leu678fs
NP_001394237.1:p.Leu732fs
NP_001394238.1:p.Leu732fs
NP_001394239.1:p.Leu732fs
NP_001394240.1:p.Leu732fs
NP_001394241.1:p.Leu431fs
NP_001394242.1:p.Leu431fs
NP_001394243.1:p.Leu205fs
NP_078951.2:p.Leu1027Alafs
NP_078951.2:p.Leu1027fs
LRG_308t1:c.3077dup
LRG_308:g.24960dup
LRG_308p1:p.Leu1027Alafs
NC_000016.9:g.23632718_23632719insA
NC_000016.9:g.23632719dup
NM_024675.3:c.3077dup
NM_024675.3:c.3077dupT

Protein change:

L1003fs

Molecular consequence:

NM_001407296.1:c.3017dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407297.1:c.3005dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407298.1:c.2915dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407299.1:c.3077dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407301.1:c.3077dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407302.1:c.2915dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407304.1:c.2192dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407305.1:c.2192dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407306.1:c.2192dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407307.1:c.2030dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407308.1:c.2192dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407309.1:c.2192dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407310.1:c.2192dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407311.1:c.2192dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407312.1:c.1289dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407313.1:c.1289dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407314.1:c.611dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024675.4:c.3077dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407300.1:c.2834+2611dup - intron variant - [Sequence Ontology: SO:0001627]

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
SCV004366252	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 12, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17200668, 17200671, 17200672, 24136930, 25099575, 28492532
SCV004930832	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Dec 20, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004366252

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 12, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV004930832

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Pathogenic
(Dec 20, 2023)

unknown

clinical testing

Citation Link

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
not provided	unknown	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004366252.1

#	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.Leu1027Alafs*26) 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

From Myriad Genetics, Inc., SCV004930832.1

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

Description

This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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

Last Updated: Sep 29, 2024

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