NM_058216.3(RAD51C):c.706-2A>G AND Breast-ovarian cancer, familial, susceptibility to, 3

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (6 submissions)
Last evaluated:: Feb 26, 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:: RCV000456123.9

Allele description

NM_058216.3(RAD51C):c.706-2A>G

Gene:

RAD51C:RAD51 paralog C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q22

Genomic location:

Preferred name:

NM_058216.3(RAD51C):c.706-2A>G

Other names:

IVS4-2A>G

HGVS:

NC_000017.11:g.58709857A>G
NG_023199.1:g.22256A>G
NM_058216.3:c.706-2A>GMANE SELECT
LRG_314t1:c.706-2A>G
LRG_314:g.22256A>G
NC_000017.10:g.56787218A>G
NM_058216.1:c.706-2A>G
NM_058216.2:c.706-2A>G

Links:

dbSNP: rs587780259

NCBI 1000 Genomes Browser:

rs587780259

Molecular consequence:

NM_058216.3:c.706-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Functional consequence:

effect on RNA splicing [Variation Ontology: 0362]

Condition(s)

Name:: Breast-ovarian cancer, familial, susceptibility to, 3
Synonyms:: RAD51C-Related Breast/Ovarian Cancer; Breast-ovarian cancer, familial 3
Identifiers:: MONDO: MONDO:0013253; MedGen: C3150659; Orphanet: 145; OMIM: 613399

Recent activity

Clear Turn Off Turn On

Homo sapiens double homeobox 5 (DUX5), mRNA
Homo sapiens double homeobox 5 (DUX5), mRNA
gi|63985969|ref|NM_012149.2|

Nucleotide
programmed cell death protein 2 isoform X1 [Homo sapiens]
programmed cell death protein 2 isoform X1 [Homo sapiens]
gi|2462608774|ref|XP_054211554.1|

Protein
Homo sapiens programmed cell death 2 (PDCD2), transcript variant 4, mRNA
Homo sapiens programmed cell death 2 (PDCD2), transcript variant 4, mRNA
gi|1889444892|ref|NM_001199462.2|

Nucleotide

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
SCV000536677	Laboratoire de Biologie et Génétique du Cancer, Centre François Baclesse	criteria provided, single submitter (Submitter's publication)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001428832	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 15, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001549328	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Pathogenic	unknown	clinical testing
SCV002762841	Centre for Mendelian Genomics, University Medical Centre Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 9, 2022)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV004017745	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely pathogenic (Apr 6, 2023)	unknown	clinical testing	Citation Link,
SCV004209762	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 26, 2024)	unknown	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	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	research
not provided	unknown	yes	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

Germline mutation in the RAD51B gene confers predisposition to breast cancer.

Golmard L, Caux-Moncoutier V, Davy G, Al Ageeli E, Poirot B, Tirapo C, Michaux D, Barbaroux C, d'Enghien CD, Nicolas A, Castéra L, Sastre-Garau X, Stern MH, Houdayer C, Stoppa-Lyonnet D.

BMC Cancer. 2013 Oct 19;13:484. doi: 10.1186/1471-2407-13-484.

PubMed [citation]

PMID:: 24139550
PMCID:: PMC4016303

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Laboratoire de Biologie et Génétique du Cancer, Centre François Baclesse, SCV000536677.1

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

From Institute of Human Genetics, University of Leipzig Medical Center, SCV001428832.2

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001549328.1

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

Description

The RAD51C c.706-2A>G variant was identified in 12 of 15014 proband chromosomes (frequency: 0.0008) from individuals or families with breast and ovarian cancer (Castera 2014, Couch 2015, Golmard 2013, Loveday 2012, Song 2015). The variant was also identified in the following databases: dbSNP (ID: rs587780259) as "With Pathogenic allele", ClinVar (5x pathogenic, 2x likely pathogenic), Clinvitae, and LOVD 3.0 (1x). The variant was not identified in Cosmic or the MutDB database. The variant was identified in control databases in 6 of 277092 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). It was observed in the European population in 6 of 126600 chromosomes (freq: 0.00005), but not in the African, Other, Latino, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. Functional studies utilizing mRNA from lymphoblastoid cell lines shows this variant affects splicing, resulting in in-frame skipping of exon 5 (Golmard 2013, Davy 2017). The c.706-2A>G variant is predicted to cause abnormal splicing because the nucleotide substitution occurs in the invariant region of the splice consensus sequence. In addition, 5 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. In summary, based on the above information this variant meets our laboratoryâ€šÃ„Ã´s criteria to be classified as pathogenic.

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

From Centre for Mendelian Genomics, University Medical Centre Ljubljana, SCV002762841.2

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

Description

PVS1, PS3, PS4_STR, PP1

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004017745.1

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

Description

This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.

#	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 Baylor Genetics, SCV004209762.2

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 17, 2024

ClinVar

Relating variation to medicine