NM_024675.4(PALB2):c.1378C>T (p.Gln460Ter) AND Familial cancer of breast

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 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:: RCV001853499.8

Allele description [Variation Report for NM_024675.4(PALB2):c.1378C>T (p.Gln460Ter)]

NM_024675.4(PALB2):c.1378C>T (p.Gln460Ter)

Gene:

PALB2:partner and localizer of BRCA2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NM_024675.4(PALB2):c.1378C>T (p.Gln460Ter)

HGVS:

NC_000016.10:g.23635168G>A
NG_007406.1:g.11190C>T
NM_024675.4:c.1378C>TMANE SELECT
NP_078951.2:p.Gln460Ter
NP_078951.2:p.Gln460Ter
LRG_308t1:c.1378C>T
LRG_308:g.11190C>T
LRG_308p1:p.Gln460Ter
NC_000016.9:g.23646489G>A
NM_024675.3:c.1378C>T

Protein change:

Q460*

Links:

dbSNP: rs876658166

NCBI 1000 Genomes Browser:

rs876658166

Molecular consequence:

NM_024675.4:c.1378C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV002240058	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 3, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 28724667, 17200668, 17200671, 17200672, 24136930, 25099575, 28492532
SCV004189469	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Sep 8, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002240058

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 3, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV004189469

Myriad Genetics, Inc.

criteria provided, single submitter

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

Pathogenic
(Sep 8, 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

Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients.

Sun J, Meng H, Yao L, Lv M, Bai J, Zhang J, Wang L, Ouyang T, Li J, Wang T, Fan Z, Fan T, Lin B, Xie Y.

Clin Cancer Res. 2017 Oct 15;23(20):6113-6119. doi: 10.1158/1078-0432.CCR-16-3227. Epub 2017 Jul 19.

PubMed [citation]

PMID:: 28724667

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

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002240058.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 229742). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 28724667). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln460*) 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).

#	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., SCV004189469.1

#	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 termination codon and is 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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