NM_024675.4(PALB2):c.2483G>A (p.Cys828Tyr) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 24, 2023
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:: RCV003585688.1

Allele description [Variation Report for NM_024675.4(PALB2):c.2483G>A (p.Cys828Tyr)]

NM_024675.4(PALB2):c.2483G>A (p.Cys828Tyr)

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.2483G>A (p.Cys828Tyr)

HGVS:

NC_000016.10:g.23629671C>T
NG_007406.1:g.16687G>A
NM_001407296.1:c.2423G>A
NM_001407297.1:c.2483G>A
NM_001407298.1:c.2483G>A
NM_001407299.1:c.2483G>A
NM_001407300.1:c.2483G>A
NM_001407301.1:c.2483G>A
NM_001407302.1:c.2483G>A
NM_001407304.1:c.1598G>A
NM_001407305.1:c.1598G>A
NM_001407306.1:c.1598G>A
NM_001407307.1:c.1598G>A
NM_001407308.1:c.1598G>A
NM_001407309.1:c.1598G>A
NM_001407310.1:c.1598G>A
NM_001407311.1:c.1598G>A
NM_001407312.1:c.695G>A
NM_001407313.1:c.695G>A
NM_001407314.1:c.49-396G>A
NM_024675.4:c.2483G>AMANE SELECT
NP_001394225.1:p.Cys808Tyr
NP_001394226.1:p.Cys828Tyr
NP_001394227.1:p.Cys828Tyr
NP_001394228.1:p.Cys828Tyr
NP_001394229.1:p.Cys828Tyr
NP_001394230.1:p.Cys828Tyr
NP_001394231.1:p.Cys828Tyr
NP_001394233.1:p.Cys533Tyr
NP_001394234.1:p.Cys533Tyr
NP_001394235.1:p.Cys533Tyr
NP_001394236.1:p.Cys533Tyr
NP_001394237.1:p.Cys533Tyr
NP_001394238.1:p.Cys533Tyr
NP_001394239.1:p.Cys533Tyr
NP_001394240.1:p.Cys533Tyr
NP_001394241.1:p.Cys232Tyr
NP_001394242.1:p.Cys232Tyr
NP_078951.2:p.Cys828Tyr
NP_078951.2:p.Cys828Tyr
LRG_308t1:c.2483G>A
LRG_308:g.16687G>A
LRG_308p1:p.Cys828Tyr
NC_000016.9:g.23640992C>T
NM_024675.3:c.2483G>A

Protein change:

C232Y

Molecular consequence:

NM_001407314.1:c.49-396G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001407296.1:c.2423G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407297.1:c.2483G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407298.1:c.2483G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407299.1:c.2483G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407300.1:c.2483G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407301.1:c.2483G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407302.1:c.2483G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407304.1:c.1598G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407305.1:c.1598G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407306.1:c.1598G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407307.1:c.1598G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407308.1:c.1598G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407309.1:c.1598G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407310.1:c.1598G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407311.1:c.1598G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407312.1:c.695G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407313.1:c.695G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024675.4:c.2483G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004357861	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 24, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 32546565, 33471991, 34130653, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004357861

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 24, 2023)

germline

clinical testing

PubMed (4)
[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

Population-based targeted sequencing of 54 candidate genes identifies PALB2 as a susceptibility gene for high-grade serous ovarian cancer.

Song H, Dicks EM, Tyrer J, Intermaggio M, Chenevix-Trench G, Bowtell DD, Traficante N, Group A, Brenton J, Goranova T, Hosking K, Piskorz A, van Oudenhove E, Doherty J, Harris HR, Rossing MA, Duerst M, Dork T, Bogdanova NV, Modugno F, Moysich K, Odunsi K, et al.

J Med Genet. 2021 May;58(5):305-313. doi: 10.1136/jmedgenet-2019-106739. Epub 2020 Jun 16.

PubMed [citation]

PMID:: 32546565
PMCID:: PMC8086250

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Breast Cancer Association Consortium., Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, Wahlström C, Pooley KA, Parsons MT, Fortuno C, Wang Q, Bolla MK, Dennis J, Keeman R, Alonso MR, Álvarez N, Herraez B, Fernandez V, Núñez-Torres R, Osorio A, Valcich J, Li M, et al.

N Engl J Med. 2021 Feb 4;384(5):428-439. doi: 10.1056/NEJMoa1913948. Epub 2021 Jan 20.

PubMed [citation]

PMID:: 33471991
PMCID:: PMC7611105

See all PubMed Citations (4)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV004357861.1

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

Description

This missense variant replaces cysteine with tyrosine at codon 828 of the PALB2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer and in a breast cancer case-control meta-analysis in 0/60466 cases and 2/53461 unaffected individuals (PMID: 33471991, 34130653; Leiden Open Variation Database DB-ID PALB2_010889). This variant also has been reported in an ovarian cancer case-control study in 1/6115 unaffected control individuals and absent in 6385 cases (PMID: 32546565). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	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: Feb 20, 2024

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