NM_058216.3(RAD51C):c.914G>A (p.Trp305Ter) AND Fanconi anemia complementation group O

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 18, 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:: RCV000541903.11

Allele description [Variation Report for NM_058216.3(RAD51C):c.914G>A (p.Trp305Ter)]

NM_058216.3(RAD51C):c.914G>A (p.Trp305Ter)

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.914G>A (p.Trp305Ter)

HGVS:

NC_000017.11:g.58724049G>A
NG_023199.1:g.36448G>A
NM_058216.3:c.914G>AMANE SELECT
NP_478123.1:p.Trp305Ter
LRG_314t1:c.914G>A
LRG_314:g.36448G>A
NC_000017.10:g.56801410G>A
NM_058216.1:c.914G>A
NM_058216.2:c.914G>A
NR_103872.2:n.789G>A

Protein change:

W305*

Links:

dbSNP: rs876659874

NCBI 1000 Genomes Browser:

rs876659874

Molecular consequence:

NR_103872.2:n.789G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_058216.3:c.914G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

Recent activity

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Rattus norvegicus Rho GTPase activating protein 24, mRNA (cDNA clone MGC:93797 I...
Rattus norvegicus Rho GTPase activating protein 24, mRNA (cDNA clone MGC:93797 IMAGE:7109913), complete cds
gi|55249718|gb|BC085797.1|

Nucleotide
AHCTF1 AT-hook containing transcription factor 1 [Gallus gallus]
AHCTF1 AT-hook containing transcription factor 1 [Gallus gallus]
Gene ID:421484

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000660370	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 18, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20400964, 21990120, 24800917, 29278735, 28492532
SCV002019630	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 14, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000660370

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 18, 2023)

germline

clinical testing

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

SCV002019630

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 14, 2019)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Analysis of RAD51C germline mutations in high-risk breast and ovarian cancer families and ovarian cancer patients.

Thompson ER, Boyle SE, Johnson J, Ryland GL, Sawyer S, Choong DY, kConFab, Chenevix-Trench G, Trainer AH, Lindeman GJ, Mitchell G, James PA, Campbell IG.

Hum Mutat. 2012 Jan;33(1):95-9. doi: 10.1002/humu.21625. Epub 2011 Nov 4.

PubMed [citation]

PMID:: 21990120

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000660370.6

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

Description

This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. For these reasons, this variant has been classified as Pathogenic. RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). ClinVar contains an entry for this variant (Variation ID: 232614). This variant is present in population databases (no rsID available, gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp305*) in the RAD51C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917, 29278735).

#	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 Revvity Omics, Revvity, SCV002019630.3

#	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

Last Updated: Oct 26, 2024

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