NM_000059.4(BRCA2):c.502C>G (p.Pro168Ala) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 22, 2024
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:: RCV001023445.3

Allele description [Variation Report for NM_000059.4(BRCA2):c.502C>G (p.Pro168Ala)]

NM_000059.4(BRCA2):c.502C>G (p.Pro168Ala)

Gene:

BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.502C>G (p.Pro168Ala)

HGVS:

NC_000013.11:g.32326268C>G
NG_012772.3:g.15789C>G
NM_000059.4:c.502C>GMANE SELECT
NP_000050.2:p.Pro168Ala
NP_000050.3:p.Pro168Ala
LRG_293t1:c.502C>G
LRG_293:g.15789C>G
LRG_293p1:p.Pro168Ala
NC_000013.10:g.32900405C>G
NM_000059.3:c.502C>G
U43746.1:n.730C>G

Protein change:

P168A

Links:

dbSNP: rs80358726

NCBI 1000 Genomes Browser:

rs80358726

Molecular consequence:

NM_000059.4:c.502C>G - 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
SCV001185322	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 22, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25503501, 29409476 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001185322

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 22, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Citations

PubMed

Prevalence of mutations in a panel of breast cancer susceptibility genes in BRCA1/2-negative patients with early-onset breast cancer.

Maxwell KN, Wubbenhorst B, D'Andrea K, Garman B, Long JM, Powers J, Rathbun K, Stopfer JE, Zhu J, Bradbury AR, Simon MS, DeMichele A, Domchek SM, Nathanson KL.

Genet Med. 2015 Aug;17(8):630-8. doi: 10.1038/gim.2014.176. Epub 2014 Dec 11.

PubMed [citation]

PMID:: 25503501
PMCID:: PMC4465412

Germline BRCA1/BRCA2 mutations among high risk breast cancer patients in Jordan.

Abdel-Razeq H, Al-Omari A, Zahran F, Arun B.

BMC Cancer. 2018 Feb 6;18(1):152. doi: 10.1186/s12885-018-4079-1.

PubMed [citation]

PMID:: 29409476
PMCID:: PMC5802063

Details of each submission

From Ambry Genetics, SCV001185322.4

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

Description

The p.P168A variant (also known as c.502C>G), located in coding exon 5 of the BRCA2 gene, results from a C to G substitution at nucleotide position 502. The proline at codon 168 is replaced by alanine, an amino acid with highly similar properties. This alteration was identified in 1/278 individuals from a cohort BRCA1/2-negative individuals with early-onset breast cancer via multiplex panel testing of 22 cancer susceptibility genes (Maxwell KN et al. Genet Med, 2015 Aug;17:630-8), and was also detected in 1/100 Jordanian breast cancer patients (Abdel-Razeq H et al. BMC Cancer, 2018 Feb;18:152). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.

#	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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