rs751528808
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1PM2
The NM_058216.3(RAD51C):c.688C>T(p.Leu230Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,459,974 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L230L) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
RAD51C
NM_058216.3 missense
NM_058216.3 missense
Scores
10
8
Clinical Significance
Conservation
PhyloP100: 3.84
Publications
1 publications found
Genes affected
RAD51C (HGNC:9820): (RAD51 paralog C) This gene is a member of the RAD51 family. RAD51 family members are highly similar to bacterial RecA and Saccharomyces cerevisiae Rad51 and are known to be involved in the homologous recombination and repair of DNA. This protein can interact with other RAD51 paralogs and is reported to be important for Holliday junction resolution. Mutations in this gene are associated with Fanconi anemia-like syndrome. This gene is one of four localized to a region of chromosome 17q23 where amplification occurs frequently in breast tumors. Overexpression of the four genes during amplification has been observed and suggests a possible role in tumor progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
RAD51C Gene-Disease associations (from GenCC):
- RAD51C-related cancer predispositionInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- breast-ovarian cancer, familial, susceptibility to, 3Inheritance: AD Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- Fanconi anemia complementation group OInheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P
- hereditary breast ovarian cancer syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Fanconi anemiaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM1
In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 29 uncertain in NM_058216.3
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_058216.3. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RAD51C | TSL:1 MANE Select | c.688C>T | p.Leu230Phe | missense | Exon 4 of 9 | ENSP00000336701.4 | O43502-1 | ||
| RAD51C | TSL:1 | n.*116C>T | non_coding_transcript_exon | Exon 3 of 8 | ENSP00000433332.1 | Q7KZJ0 | |||
| RAD51C | TSL:1 | n.*116C>T | 3_prime_UTR | Exon 3 of 8 | ENSP00000433332.1 | Q7KZJ0 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251194 AF XY: 0.00000736 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
251194
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1459974Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726454 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1459974
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
726454
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33438
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26122
East Asian (EAS)
AF:
AC:
0
AN:
39616
South Asian (SAS)
AF:
AC:
1
AN:
86196
European-Finnish (FIN)
AF:
AC:
0
AN:
53194
Middle Eastern (MID)
AF:
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1110592
Other (OTH)
AF:
AC:
0
AN:
60338
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.542
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
31
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
1
EpiCase
AF:
EpiControl
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Conflicting classifications of pathogenicity
Revision:criteria provided, conflicting classifications
Pathogenic
VUS
Benign
Condition
-
2
-
Hereditary cancer-predisposing syndrome (2)
-
-
1
Breast-ovarian cancer, familial, susceptibility to, 2 (1)
-
1
-
Fanconi anemia complementation group O (1)
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1
-
Fanconi anemia complementation group O;C3150659:Breast-ovarian cancer, familial, susceptibility to, 3 (1)
-
1
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of helix (P = 0.0017)
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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