NM_058216.3(RAD51C):c.404+2T>C AND Fanconi anemia complementation group O

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 16, 2024
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:: RCV000467500.11

Allele description [Variation Report for NM_058216.3(RAD51C):c.404+2T>C]

NM_058216.3(RAD51C):c.404+2T>C

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.404+2T>C

Other names:

*136Q

HGVS:

NC_000017.11:g.58695191T>C
NG_023199.1:g.7590T>C
NG_047169.1:g.1889A>G
NM_002876.4:c.406T>C
NM_058216.3:c.404+2T>CMANE SELECT
NP_002867.1:p.Ter136Gln
LRG_314t1:c.404+2T>C
LRG_314:g.7590T>C
NC_000017.10:g.56772552T>C
NM_002876.2:c.406T>C
NM_058216.1:c.404+2T>C
NM_058216.2:c.404+2T>C
NR_103873.1:n.374T>C

Links:

dbSNP: rs730881931

NCBI 1000 Genomes Browser:

rs730881931

Molecular consequence:

NR_103873.1:n.374T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_058216.3:c.404+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_002876.4:c.406T>C - stop lost - [Sequence Ontology: SO:0001578]

Condition(s)

Name:: Fanconi anemia complementation group O
Identifiers:: MONDO: MONDO:0013248; MedGen: C3150653; Orphanet: 84; OMIM: 613390

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000550176	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 16, 2024)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 16199547, 20400964, 21990120, 24800917, 29278735, 26681312, 32107557, 33277227, 35740625, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000550176

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 16, 2024)

germline

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene.

Meindl A, Hellebrand H, Wiek C, Erven V, Wappenschmidt B, Niederacher D, Freund M, Lichtner P, Hartmann L, Schaal H, Ramser J, Honisch E, Kubisch C, Wichmann HE, Kast K, Deissler H, Engel C, Müller-Myhsok B, Neveling K, Kiechle M, Mathew CG, Schindler D, et al.

Nat Genet. 2010 May;42(5):410-4. doi: 10.1038/ng.569. Epub 2010 Apr 18.

PubMed [citation]

PMID:: 20400964

See all PubMed Citations (10)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000550176.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This sequence change affects a donor splice site in intron 2 of the RAD51C gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917, 29278735). This variant is present in population databases (rs730881931, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with breast cancer and/or ovarian cancer (PMID: 26681312, 32107557, 33277227). ClinVar contains an entry for this variant (Variation ID: 182835). Studies have shown that disruption of this splice site alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 35740625). For these reasons, this variant has been 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

Last Updated: Sep 29, 2024

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Relating variation to medicine