NM_024675.4(PALB2):c.1984A>T (p.Lys662Ter) AND Familial cancer of breast

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 12, 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:: RCV000635787.10

Allele description [Variation Report for NM_024675.4(PALB2):c.1984A>T (p.Lys662Ter)]

NM_024675.4(PALB2):c.1984A>T (p.Lys662Ter)

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.1984A>T (p.Lys662Ter)

HGVS:

NC_000016.10:g.23630170T>A
NG_007406.1:g.16188A>T
NM_024675.4:c.1984A>TMANE SELECT
NP_078951.2:p.Lys662Ter
NP_078951.2:p.Lys662Ter
LRG_308t1:c.1984A>T
LRG_308:g.16188A>T
LRG_308p1:p.Lys662Ter
NC_000016.9:g.23641491T>A
NM_024675.3:c.1984A>T

Protein change:

K662*

Links:

dbSNP: rs1555460533

NCBI 1000 Genomes Browser:

rs1555460533

Molecular consequence:

NM_024675.4:c.1984A>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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Homo sapiens ARP6 actin-related protein 6 homolog (yeast), mRNA (cDNA clone IMAGE:3923638), with apparent retained intron
gi|30048176|gb|BC050679.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000757210	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 5, 2018)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 25575445, 27648926, 17200668, 24136930, 25099575, 28492532
SCV004186120	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Sep 12, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000757210

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 5, 2018)

germline

clinical testing

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

SCV004186120

Myriad Genetics, Inc.

criteria provided, single submitter

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

Pathogenic
(Sep 12, 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

Mutation screening of PALB2 in clinically ascertained families from the Breast Cancer Family Registry.

Nguyen-Dumont T, Hammet F, Mahmoodi M, Tsimiklis H, Teo ZL, Li R, Pope BJ, Terry MB, Buys SS, Daly M, Hopper JL, Winship I, Goldgar DE, Park DJ, Southey MC.

Breast Cancer Res Treat. 2015 Jan;149(2):547-54. doi: 10.1007/s10549-014-3260-8. Epub 2015 Jan 10.

PubMed [citation]

PMID:: 25575445
PMCID:: PMC4542063

Whole-exome sequencing and targeted gene sequencing provide insights into the role of PALB2 as a male breast cancer susceptibility gene.

Silvestri V, Zelli V, Valentini V, Rizzolo P, Navazio AS, Coppa A, Agata S, Oliani C, Barana D, Castrignanò T, Viel A, Russo A, Tibiletti MG, Zanna I, Masala G, Cortesi L, Manoukian S, Azzollini J, Peissel B, Bonanni B, Peterlongo P, Radice P, et al.

Cancer. 2017 Jan 1;123(2):210-218. doi: 10.1002/cncr.30337. Epub 2016 Sep 20.

PubMed [citation]

PMID:: 27648926

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000757210.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This variant has been reported in individuals with a personal and/or family history of breast and other cancers (PMID: 25575445, 27648926). This sequence change creates a premature translational stop signal (p.Lys662*) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 24136930, 25099575). 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., SCV004186120.1

#	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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