NM_024675.4(PALB2):c.3082G>C (p.Gly1028Arg) AND Familial cancer of breast

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 25, 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:: RCV003607639.2

Allele description [Variation Report for NM_024675.4(PALB2):c.3082G>C (p.Gly1028Arg)]

NM_024675.4(PALB2):c.3082G>C (p.Gly1028Arg)

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.3082G>C (p.Gly1028Arg)

HGVS:

NC_000016.10:g.23621393C>G
NG_007406.1:g.24965G>C
NM_001407296.1:c.3022G>C
NM_001407297.1:c.3010G>C
NM_001407298.1:c.2920G>C
NM_001407299.1:c.3082G>C
NM_001407300.1:c.2834+2616G>C
NM_001407301.1:c.3082G>C
NM_001407302.1:c.2920G>C
NM_001407304.1:c.2197G>C
NM_001407305.1:c.2197G>C
NM_001407306.1:c.2197G>C
NM_001407307.1:c.2035G>C
NM_001407308.1:c.2197G>C
NM_001407309.1:c.2197G>C
NM_001407310.1:c.2197G>C
NM_001407311.1:c.2197G>C
NM_001407312.1:c.1294G>C
NM_001407313.1:c.1294G>C
NM_001407314.1:c.616G>C
NM_024675.4:c.3082G>CMANE SELECT
NP_001394225.1:p.Gly1008Arg
NP_001394226.1:p.Gly1004Arg
NP_001394227.1:p.Gly974Arg
NP_001394228.1:p.Gly1028Arg
NP_001394230.1:p.Gly1028Arg
NP_001394231.1:p.Gly974Arg
NP_001394233.1:p.Gly733Arg
NP_001394234.1:p.Gly733Arg
NP_001394235.1:p.Gly733Arg
NP_001394236.1:p.Gly679Arg
NP_001394237.1:p.Gly733Arg
NP_001394238.1:p.Gly733Arg
NP_001394239.1:p.Gly733Arg
NP_001394240.1:p.Gly733Arg
NP_001394241.1:p.Gly432Arg
NP_001394242.1:p.Gly432Arg
NP_001394243.1:p.Gly206Arg
NP_078951.2:p.Gly1028Arg
NP_078951.2:p.Gly1028Arg
LRG_308t1:c.3082G>C
LRG_308:g.24965G>C
LRG_308p1:p.Gly1028Arg
NC_000016.9:g.23632714C>G
NM_024675.3:c.3082G>C

Protein change:

G1004R

Molecular consequence:

NM_001407300.1:c.2834+2616G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407296.1:c.3022G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407297.1:c.3010G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407298.1:c.2920G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407299.1:c.3082G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407301.1:c.3082G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407302.1:c.2920G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407304.1:c.2197G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407305.1:c.2197G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407306.1:c.2197G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407307.1:c.2035G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407308.1:c.2197G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407309.1:c.2197G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407310.1:c.2197G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407311.1:c.2197G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407312.1:c.1294G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407313.1:c.1294G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407314.1:c.616G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_024675.4:c.3082G>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV004376639	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 25, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33646313, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004376639

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 25, 2023)

germline

clinical testing

PubMed (2)
[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

Gene Sequencing for Pathogenic Variants Among Adults With Breast and Ovarian Cancer in the Caribbean.

George SHL, Donenberg T, Alexis C, DeGennaro V Jr, Dyer H, Yin S, Ali J, Butler R, Chin SN, Curling D, Lowe D, Lunn J, Turnquest T, Wharfe G, Cerbon D, Barreto-Coelho P, Schlumbrecht MP, Akbari MR, Narod SA, Hurley JE.

JAMA Netw Open. 2021 Mar 1;4(3):e210307. doi: 10.1001/jamanetworkopen.2021.0307.

PubMed [citation]

PMID:: 33646313
PMCID:: PMC7921902

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004376639.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PALB2 protein function. This missense change has been observed in individual(s) with breast cancer (PMID: 33646313). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1028 of the PALB2 protein (p.Gly1028Arg).

#	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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