NM_000059.4(BRCA2):c.9898C>T (p.Pro3300Ser) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 23, 2022
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:: RCV001019864.3

Allele description [Variation Report for NM_000059.4(BRCA2):c.9898C>T (p.Pro3300Ser)]

NM_000059.4(BRCA2):c.9898C>T (p.Pro3300Ser)

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.9898C>T (p.Pro3300Ser)

HGVS:

NC_000013.11:g.32398411C>T
NG_012772.3:g.87932C>T
NM_000059.4:c.9898C>TMANE SELECT
NP_000050.2:p.Pro3300Ser
NP_000050.3:p.Pro3300Ser
LRG_293t1:c.9898C>T
LRG_293:g.87932C>T
LRG_293p1:p.Pro3300Ser
NC_000013.10:g.32972548C>T
NM_000059.3:c.9898C>T

Protein change:

P3300S

Links:

dbSNP: rs770868371

NCBI 1000 Genomes Browser:

rs770868371

Molecular consequence:

NM_000059.4:c.9898C>T - 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

Recent activity

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Human SWI/SNF complex 60 KDa subunit (BAF60a) mRNA, alternatively spliced, compl...
Human SWI/SNF complex 60 KDa subunit (BAF60a) mRNA, alternatively spliced, complete cds
gi|1549242|gb|U66617.1|HSU66617

Nucleotide
SRP311843 (12)
SRA
glycosyltransferase family 39 protein [Butyricimonas virosa]
glycosyltransferase family 39 protein [Butyricimonas virosa]
gi|1985997779|gnl|PRJNA231221|I6J59 0|gb|QRO50573.1|

Protein
glycoside hydrolase family 43 protein [Phocaeicola vulgatus]
glycoside hydrolase family 43 protein [Phocaeicola vulgatus]
gi|1966886532|gnl|PRJNA231221|I6I55 5|gb|QQY39894.1|

Protein
Gm9864 AND (alive[prop]) (0)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001181273	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (May 23, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001181273

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(May 23, 2022)

germline

clinical testing

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

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

Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.

Momozawa Y, Iwasaki Y, Parsons MT, Kamatani Y, Takahashi A, Tamura C, Katagiri T, Yoshida T, Nakamura S, Sugano K, Miki Y, Hirata M, Matsuda K, Spurdle AB, Kubo M.

Nat Commun. 2018 Oct 4;9(1):4083. doi: 10.1038/s41467-018-06581-8.

PubMed [citation]

PMID:: 30287823
PMCID:: PMC6172276

Details of each submission

From Ambry Genetics, SCV001181273.4

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

Description

The p.P3300S variant (also known as c.9898C>T), located in coding exon 26 of the BRCA2 gene, results from a C to T substitution at nucleotide position 9898. The proline at codon 3300 is replaced by serine, an amino acid with similar properties. This alteration has been detected in Chinese breast cancer and esophageal cancer patients as well as in a healthy, unaffected Chinese individual (Hu N et al. Clin Cancer Res. 2002 Apr;8(4):1121-6; Hu N et al. Cancer Detect Prev. 2003;27(2):132-8; Li G et al. J Cancer Res Clin Oncol. 2017 Oct;143(10):2011-2024). Additionally, this alteration has not been reported in 7051 unselected breast cancer patients and 0.00009 in 11241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, 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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