NM_024675.4(PALB2):c.1510G>C (p.Val504Leu) AND Familial cancer of breast

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 22, 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:: RCV003608159.2

Allele description [Variation Report for NM_024675.4(PALB2):c.1510G>C (p.Val504Leu)]

NM_024675.4(PALB2):c.1510G>C (p.Val504Leu)

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.1510G>C (p.Val504Leu)

HGVS:

NC_000016.10:g.23635036C>G
NG_007406.1:g.11322G>C
NM_001407296.1:c.1450G>C
NM_001407297.1:c.1510G>C
NM_001407298.1:c.1510G>C
NM_001407299.1:c.1510G>C
NM_001407300.1:c.1510G>C
NM_001407301.1:c.1510G>C
NM_001407302.1:c.1510G>C
NM_001407304.1:c.625G>C
NM_001407305.1:c.625G>C
NM_001407306.1:c.625G>C
NM_001407307.1:c.625G>C
NM_001407308.1:c.625G>C
NM_001407309.1:c.625G>C
NM_001407310.1:c.625G>C
NM_001407311.1:c.625G>C
NM_001407312.1:c.-104-4567G>C
NM_001407313.1:c.-104-4567G>C
NM_001407314.1:c.49-5761G>C
NM_024675.4:c.1510G>CMANE SELECT
NP_001394225.1:p.Val484Leu
NP_001394226.1:p.Val504Leu
NP_001394227.1:p.Val504Leu
NP_001394228.1:p.Val504Leu
NP_001394229.1:p.Val504Leu
NP_001394230.1:p.Val504Leu
NP_001394231.1:p.Val504Leu
NP_001394233.1:p.Val209Leu
NP_001394234.1:p.Val209Leu
NP_001394235.1:p.Val209Leu
NP_001394236.1:p.Val209Leu
NP_001394237.1:p.Val209Leu
NP_001394238.1:p.Val209Leu
NP_001394239.1:p.Val209Leu
NP_001394240.1:p.Val209Leu
NP_078951.2:p.Val504Leu
NP_078951.2:p.Val504Leu
LRG_308t1:c.1510G>C
LRG_308:g.11322G>C
LRG_308p1:p.Val504Leu
NC_000016.9:g.23646357C>G
NM_024675.3:c.1510G>C

Protein change:

V209L

Molecular consequence:

NM_001407312.1:c.-104-4567G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407313.1:c.-104-4567G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407314.1:c.49-5761G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407296.1:c.1450G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407297.1:c.1510G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407298.1:c.1510G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407299.1:c.1510G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407300.1:c.1510G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407301.1:c.1510G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407302.1:c.1510G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407304.1:c.625G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407305.1:c.625G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407306.1:c.625G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407307.1:c.625G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407308.1:c.625G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407309.1:c.625G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407310.1:c.625G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407311.1:c.625G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_024675.4:c.1510G>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

Recent activity

Clear Turn Off Turn On

adenosine 3'-phospho 5'-phosphosulfate transporter 1 isoform X3 [Zalophus califo...
adenosine 3'-phospho 5'-phosphosulfate transporter 1 isoform X3 [Zalophus californianus]
gi|1886088083|ref|XP_027457524.2|

Protein
za45d01.r1 Soares fetal liver spleen 1NFLS Homo sapiens cDNA clone IMAGE:295489 ...
za45d01.r1 Soares fetal liver spleen 1NFLS Homo sapiens cDNA clone IMAGE:295489 5', mRNA sequence
gi|1300362|gnl|dbEST|530612|gb|W235

Nucleotide
Doto coronata voucher NTNU VM-76153 cytochrome c oxidase subunit I (COX1) gene, ...
Doto coronata voucher NTNU VM-76153 cytochrome c oxidase subunit I (COX1) gene, partial cds; mitochondrial
gi|2085611606|gb|MZ902317.1|

Nucleotide
Doto coronata voucher NTNU VM-66924 cytochrome c oxidase subunit I (COX1) gene, ...
Doto coronata voucher NTNU VM-66924 cytochrome c oxidase subunit I (COX1) gene, partial cds; mitochondrial
gi|2085611562|gb|MZ902306.1|

Nucleotide
Profile neighbors for GEO Profiles (Select 61681398) (26)
GEO Profiles

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004504948	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 22, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004504948

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 22, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV004504948.1

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

Description

This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 504 of the PALB2 protein (p.Val504Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. 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 not expected to disrupt PALB2 protein function. 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.

#	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

ClinVar

Relating variation to medicine