NM_058216.3(RAD51C):c.890_899del (p.Leu297fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Oct 1, 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:: RCV000569137.9

Allele description [Variation Report for NM_058216.3(RAD51C):c.890_899del (p.Leu297fs)]

NM_058216.3(RAD51C):c.890_899del (p.Leu297fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

17q22

Genomic location:

Preferred name:

NM_058216.3(RAD51C):c.890_899del (p.Leu297fs)

HGVS:

NC_000017.10:g.56798156_56798165del
NC_000017.11:g.58720798_58720807del
NG_023199.1:g.33197_33206del
NM_058216.3:c.890_899delMANE SELECT
NP_478123.1:p.Leu297fs
LRG_314:g.33197_33206del
NC_000017.10:g.56798156_56798165del
NC_000017.10:g.56798156_56798165delTGCTTGTTCC
NC_000017.10:g.56798159_56798168del
NM_058216.1:c.890_899del
NM_058216.1:c.890_899delTTGTTCCTGC
NM_058216.2:c.890_899del
NM_058216.2:c.890_899delTTGTTCCTGC
NM_058216.3:c.890_899del
NM_058216.3:c.890_899delTTGTTCCTGCMANE SELECT
NR_103872.2:n.765_774del

Protein change:

L297fs

Links:

dbSNP: rs1555602141

NCBI 1000 Genomes Browser:

rs1555602141

Molecular consequence:

NM_058216.3:c.890_899del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_103872.2:n.765_774del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV000671900	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Pathogenic (May 3, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29255180, 29659569 Citation Link,
SCV001347925	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 1, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 25980754, 29255180, 29659569, 33326660, 25741868
SCV002530028	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Pathogenic (Dec 20, 2021)	germline	curation	PubMed (6) [See all records that cite these PMIDs] 25980754, 29659569, 33326660, 29255180, 33258288, 20400964 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000671900

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Pathogenic
(May 3, 2023)

germline

clinical testing

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

Citation Link,

SCV001347925

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 1, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV002530028

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Pathogenic
(Dec 20, 2021)

germline

curation

PubMed (6)
[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, curation

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

Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome.

Yurgelun MB, Allen B, Kaldate RR, Bowles KR, Judkins T, Kaushik P, Roa BB, Wenstrup RJ, Hartman AR, Syngal S.

Gastroenterology. 2015 Sep;149(3):604-13.e20. doi: 10.1053/j.gastro.2015.05.006. Epub 2015 May 14.

PubMed [citation]

PMID:: 25980754
PMCID:: PMC4550537

See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV000671900.5

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

Description

The c.890_899del10 pathogenic mutation, located in coding exon 6 of the RAD51C gene, results from a deletion of 10 nucleotides at nucleotide positions 890 to 899, causing a translational frameshift with a predicted alternate stop codon (p.L297Hfs*2). This alteration has been identified in a cohort of 2649 consecutive cases of breast and/or ovarian cancer and in an individual diagnosed with prostate cancer (Golmard L et al. Eur. J. Hum. Genet., 2017 12;25:1345-1353; Paulo P et al. PLoS Genet., 2018 04;14:e1007355). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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 Color Diagnostics, LLC DBA Color Health, SCV001347925.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant deletes 10 nucleotides in exon 6 of the RAD51C gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in one individual each affected with ovarian cancer (PMID: 29255180), breast and ovarian cancer (PMID: 33326660), bladder and prostate cancer (PMID: 29659569) and an individual affected with Lynch syndrome-associated cancer and/or polyps (PMID: 25980754). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of RAD51C function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

#	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 Sema4, Sema4, SCV002530028.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (6)

#	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: Apr 15, 2024

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