NM_024675.4(PALB2):c.2521del (p.Thr841fs) AND Familial cancer of breast

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 22, 2024
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:: RCV003500504.2

Allele description [Variation Report for NM_024675.4(PALB2):c.2521del (p.Thr841fs)]

NM_024675.4(PALB2):c.2521del (p.Thr841fs)

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.2521del (p.Thr841fs)

Other names:

NM_024675.3:c.2521del

HGVS:

NC_000016.10:g.23629271del
NG_007406.1:g.17089del
NM_024675.4:c.2521delMANE SELECT
NP_078951.2:p.Thr841fs
LRG_308:g.17089del
NC_000016.9:g.23640590del
NC_000016.9:g.23640592del

Protein change:

T841fs

Links:

dbSNP: rs180177116

NCBI 1000 Genomes Browser:

rs180177116

Molecular consequence:

NM_024675.4:c.2521del - 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
SCV004297695	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 22, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17200668, 17200672, 24136930, 25099575, 17200671, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004297695

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 22, 2024)

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

Fanconi anemia is associated with a defect in the BRCA2 partner PALB2.

Xia B, Dorsman JC, Ameziane N, de Vries Y, Rooimans MA, Sheng Q, Pals G, Errami A, Gluckman E, Llera J, Wang W, Livingston DM, Joenje H, de Winter JP.

Nat Genet. 2007 Feb;39(2):159-61. Epub 2006 Dec 31.

PubMed [citation]

PMID:: 17200672

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004297695.1

#	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.Thr841Glnfs*10) 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 premature translational stop signal has been observed in individual(s) with PALB2-related conditions (PMID: 17200671). ClinVar contains an entry for this variant (Variation ID: 126659). 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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