NM_024675.4(PALB2):c.1824dup (p.Ile609fs) AND Familial cancer of breast

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 13, 2024
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:: RCV001237618.7

Allele description [Variation Report for NM_024675.4(PALB2):c.1824dup (p.Ile609fs)]

NM_024675.4(PALB2):c.1824dup (p.Ile609fs)

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.1824dup (p.Ile609fs)

HGVS:

NC_000016.10:g.23630330dup
NG_007406.1:g.16028dup
NM_024675.4:c.1824dupMANE SELECT
NP_078951.2:p.Ile609fs
LRG_308t1:c.1824dup
LRG_308:g.16028dup
NC_000016.9:g.23641650_23641651insA
NC_000016.9:g.23641651dup
NM_024675.3:c.1824dup

Protein change:

I609fs

Links:

dbSNP: rs1966865368

NCBI 1000 Genomes Browser:

rs1966865368

Molecular consequence:

NM_024675.4:c.1824dup - 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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57472281[uid] AND (alive[prop]) (0)
Gene
BC037438 cDNA sequence BC037438 [Mus musculus]
BC037438 cDNA sequence BC037438 [Mus musculus]
Gene ID:403345

Gene
BC037438 AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001410384	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 11, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17200668, 24136930, 25099575, 28492532
SCV004930924	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Feb 13, 2024)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001410384

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 11, 2019)

germline

clinical testing

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

SCV004930924

Myriad Genetics, Inc.

criteria provided, single submitter

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

Pathogenic
(Feb 13, 2024)

unknown

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
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 Invitae, SCV001410384.5

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

Description

This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ile609Tyrfs*8) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with PALB2-related conditions. 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).

#	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., SCV004930924.1

#	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 8, 2024

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