NM_000059.4(BRCA2):c.9117G>A (p.Pro3039=) AND not provided

Germline classification:: Pathogenic (7 submissions)
Last evaluated:: Jun 17, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000074560.32

Allele description [Variation Report for NM_000059.4(BRCA2):c.9117G>A (p.Pro3039=)]

NM_000059.4(BRCA2):c.9117G>A (p.Pro3039=)

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.9117G>A (p.Pro3039=)

Other names:

P3039P; p.P3039P:CCG>CCA; NM_000059.4(BRCA2):c.9117G>A; p.Pro3039=

HGVS:

NC_000013.11:g.32379913G>A
NG_012772.3:g.69434G>A
NM_000059.4:c.9117G>AMANE SELECT
NP_000050.2:p.Pro3039=
NP_000050.3:p.Pro3039=
LRG_293t1:c.9117G>A
LRG_293:g.69434G>A
LRG_293p1:p.Pro3039=
NC_000013.10:g.32954050G>A
NM_000059.3:c.9117G>A
U43746.1:n.9345G>A
p.P3039P

Nucleotide change:

9345G>A

Links:

dbSNP: rs28897756

NCBI 1000 Genomes Browser:

rs28897756

Molecular consequence:

NM_000059.4:c.9117G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000108645	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 17, 2024)	germline	clinical testing	Citation Link,
SCV000296758	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Aug 6, 2019)	unknown	clinical testing	PubMed (25) [See all records that cite these PMIDs] 18375895, 10638982, 22632462, 17924331, 21990134, 23451180, 22505045, 23035815, 17011978, 28724667, 28477318, 27060066, 25186627, 28825054, 29176636, 29907814, 30702160, 30787465, 31143373, 31447099, 31825140, 32658311, 32853339, 26467025, 26295337
SCV001450340	Clinical Genetics and Genomics, Karolinska University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 3, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001906367	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001955049	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV002021530	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 26, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004027489	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 15, 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	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical classification of BRCA1 and BRCA2 DNA sequence variants: the value of cytokeratin profiles and evolutionary analysis--a report from the kConFab Investigators.

Spurdle AB, Lakhani SR, Healey S, Parry S, Da Silva LM, Brinkworth R, Hopper JL, Brown MA, Babikyan D, Chenevix-Trench G, Tavtigian SV, Goldgar DE; kConFab Investigators.

J Clin Oncol. 2008 Apr 1;26(10):1657-63. doi: 10.1200/JCO.2007.13.2779.

PubMed [citation]

PMID:: 18375895

Screening for BRCA2 mutations in 81 Dutch breast-ovarian cancer families.

Peelen T, van Vliet M, Bosch A, Bignell G, Vasen HF, Klijn JG, Meijers-Heijboer H, Stratton M, van Ommen GJ, Cornelisse CJ, Devilee P.

Br J Cancer. 2000 Jan;82(1):151-6.

PubMed [citation]

PMID:: 10638982
PMCID:: PMC2363204

See all PubMed Citations (26)

Details of each submission

From GeneDx, SCV000108645.19

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

Description

Alters the last nucleotide of the exon and has been demonstrated to cause aberrant splicing, predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease (PMID: 10638982, 17011978, 22632462, 23451180, 25382762); Multifactorial studies suggest this variant is associated with breast and ovarian cancer (PMID: 17924331, 21990134); Published functional studies demonstrate a damaging effect: reduced homology-directed repair (HDR) activity (PMID: 32398771); Observed in multiple breast/ovarian cancer families (PMID: 10638982, 17148771, 22923021, 24156927, 26026974, 28477318, 28724667); Not observed at significant frequency in large population cohorts (gnomAD); Also known as 9345G>A; This variant is associated with the following publications: (PMID: 22798144, 17011978, 22505045, 22632462, 26026974, 25948282, 33309985, 36367610, 35142179, 36881271, 36243179, 34887416, 36113475, 37310942, 35864222, 28477318, 29084914, 34413315, 38075165, 29922827, 28888541, 31447099, 32658311, 17924331, 23451180, 23035815, 22923021, 17148771, 20507642, 22217648, 18375895, 10638982, 9133456, 21324516, 18821011, 25556971, 28008555, 24156927, 27000661, 21702907, 28740454, 28873162, 27271530, 25186627, 28724667, 29805665, 29907814, 29339979, 28825054, 30702160, 31957001, 31143373, 29176636, 31825140, 31892343, 31723001, 35273153, 34645131, 33804961, 34808016, 32338768, 32393398, 32853339, 30787465, 36988593, 36000185, 25382762, 21990134, 32398771)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000296758.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (25)

Description

It has been reported in individuals affected with breast and/or ovarian cancer in the published literature (PMID: 10638982 (2000), 17011978 (2006), 17924331 (2007), 22505045 (2012), 21990134 (2012), 23451180 (2013), 28724667 (2017)). Furthermore, experimental studies have shown that the variant causes the skipping of exon 23, resulting in premature termination in protein synthesis (PMID: 22505045 (2012), 22632462 (2012), 23451180 (2013), and 27060066 (2016)). Based on the available information, the variant is classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics and Genomics, Karolinska University Hospital, SCV001450340.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute - VKGL Data-share Consensus, SCV001906367.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001955049.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002021530.3

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

#	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

From Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, SCV004027489.1

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

#	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: Nov 24, 2024

Relating variation to medicine