NM_024675.4(PALB2):c.1647del (p.His549fs) AND Familial cancer of breast

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 8, 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:: RCV003452288.3

Allele description [Variation Report for NM_024675.4(PALB2):c.1647del (p.His549fs)]

NM_024675.4(PALB2):c.1647del (p.His549fs)

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.1647del (p.His549fs)

HGVS:

NC_000016.10:g.23634899del
NG_007406.1:g.11459del
NM_001407296.1:c.1587del
NM_001407297.1:c.1647del
NM_001407298.1:c.1647del
NM_001407299.1:c.1647del
NM_001407300.1:c.1647del
NM_001407301.1:c.1647del
NM_001407302.1:c.1647del
NM_001407304.1:c.762del
NM_001407305.1:c.762del
NM_001407306.1:c.762del
NM_001407307.1:c.762del
NM_001407308.1:c.762del
NM_001407309.1:c.762del
NM_001407310.1:c.762del
NM_001407311.1:c.762del
NM_001407312.1:c.-104-4430del
NM_001407313.1:c.-104-4430del
NM_001407314.1:c.49-5624del
NM_024675.4:c.1647delMANE SELECT
NP_001394225.1:p.His529fs
NP_001394226.1:p.His549fs
NP_001394227.1:p.His549fs
NP_001394228.1:p.His549fs
NP_001394229.1:p.His549fs
NP_001394230.1:p.His549fs
NP_001394231.1:p.His549fs
NP_001394233.1:p.His254fs
NP_001394234.1:p.His254fs
NP_001394235.1:p.His254fs
NP_001394236.1:p.His254fs
NP_001394237.1:p.His254fs
NP_001394238.1:p.His254fs
NP_001394239.1:p.His254fs
NP_001394240.1:p.His254fs
NP_078951.2:p.His549Glnfs
NP_078951.2:p.His549fs
LRG_308t1:c.1647del
LRG_308:g.11459del
LRG_308p1:p.His549Glnfs
NC_000016.9:g.23646220del
NM_024675.3:c.1647delC

Protein change:

H254fs

Molecular consequence:

NM_001407296.1:c.1587del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407297.1:c.1647del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407298.1:c.1647del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407299.1:c.1647del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407300.1:c.1647del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407301.1:c.1647del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407302.1:c.1647del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407304.1:c.762del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407305.1:c.762del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407306.1:c.762del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407307.1:c.762del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407308.1:c.762del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407309.1:c.762del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407310.1:c.762del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407311.1:c.762del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024675.4:c.1647del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407312.1:c.-104-4430del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407313.1:c.-104-4430del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407314.1:c.49-5624del - 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
SCV004186251	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Sep 11, 2023)	unknown	clinical testing	Citation Link,
SCV004254445	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 8, 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

SCV004186251

Myriad Genetics, Inc.

criteria provided, single submitter

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

Pathogenic
(Sep 11, 2023)

unknown

clinical testing

Citation Link,

SCV004254445

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 8, 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
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 Myriad Genetics, Inc., SCV004186251.1

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004254445.1

#	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.His549Glnfs*12) 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: Sep 29, 2024

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