NM_058216.3(RAD51C):c.774del (p.Thr259fs) AND Breast-ovarian cancer, familial, susceptibility to, 3

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Apr 5, 2023
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:: RCV001250429.4

Allele description [Variation Report for NM_058216.3(RAD51C):c.774del (p.Thr259fs)]

NM_058216.3(RAD51C):c.774del (p.Thr259fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

17q22

Genomic location:

Preferred name:

NM_058216.3(RAD51C):c.774del (p.Thr259fs)

HGVS:

NC_000017.11:g.58709927del
NG_023199.1:g.22326del
NM_058216.3:c.774delMANE SELECT
NP_478123.1:p.Thr259fs
LRG_314t1:c.774del
LRG_314:g.22326del
NC_000017.10:g.56787288del
NM_058216.1:c.774del
NM_058216.1:c.774delT
NM_058216.2:c.774del
NM_058216.2:c.774delT
NM_058216.3:c.774delTMANE SELECT
NR_103872.2:n.649del

Protein change:

T259fs

Links:

dbSNP: rs754367349

NCBI 1000 Genomes Browser:

rs754367349

Molecular consequence:

NM_058216.3:c.774del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_103872.2:n.649del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001424790	Division of Medical Genetics, University of Washington - CSER_CHARM	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 10, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002589014	BRCAlab, Lund University	no assertion criteria provided	Pathogenic (Aug 26, 2022)	germline	clinical testing
SCV004019971	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Apr 5, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001424790

Division of Medical Genetics, University of Washington - CSER_CHARM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 10, 2019)

germline

clinical testing

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

SCV002589014

BRCAlab, Lund University

no assertion criteria provided

Pathogenic
(Aug 26, 2022)

germline

clinical testing

SCV004019971

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Pathogenic
(Apr 5, 2023)

unknown

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	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
not provided	germline	yes	not provided	4	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Division of Medical Genetics, University of Washington - CSER_CHARM, SCV001424790.1

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

Description

This variant leads to a translational frameshift and the introduction of a premature termination codon four residues downstream. The variant transcript is predicted to be unstable and degraded by nonsense-mediated decay. Loss of expression of one allele of RAD51C is a well-established mechanism of disease for increased ovarian cancer risk [Romero 2011, Vuorela 2011, Song 2015]. This variant has been reported in individuals with breast and ovarian cancer [Meindl 2010, Thompson 2012, Rashid 2014]. This variant has a combined allele frequency of 0.000045 in the Broad Institute gnomAD Browser (https://gnomad.broadinstitute.org/). Thus, this variant is interpreted as likely pathogenic.

#	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 BRCAlab, Lund University, SCV002589014.1

#	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	4	not provided

From Myriad Genetics, Inc., SCV004019971.1

#	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 pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

#	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: Mar 29, 2025

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