About RAD51C
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
RAD51C c.431T>C, p.(Ile144Thr)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen RAD51C VCEP v1.0.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
NM_058216.3:c.431T>C is at extremely low frequency in population databases. gnomAD v2.1: AF=0.00566% (16/282,878 alleles, 0 homozygotes). gnomAD v4.1: AF=0.01419% (229/1,614,096 alleles, 0 homozygotes). Both overall frequencies are well below the 0.1% threshold. No homozygotes observed. Note: gnomAD v4.1 grpmax FAF=0.178% and Middle Eastern subpopulation AF=0.279%, which slightly moderates the strength but remains below the BS1 threshold of 0.3%.
Benign criteria applied · 1
BP6Supporting
BP6 · supporting
Myriad Genetics, Inc. (SCV004019909) classified this variant as Likely benign with criteria provided. This represents a reputable clinical laboratory asserting a benign interpretation. While only a single submitter, it meets BP6 at supporting level.
Recorded classification: Uncertain significance
ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RAD51C Version 1.0.0 v1.0.0 lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BP6 supporting; combination = 1 supporting + 1 supporting benign, which maps to VUS.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
229 / 1,614,096 alleles
gnomAD v4.1: 229 / 1,614,096 alleles. Recorded AF 0.000141875. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 5.65615e-05; MAF= 0.00566%, 16/282878 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000240308; MAF= 0.02403%, 6/24968 alleles, homozygotes = 0); grpmax FAF= 0.00015629.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
19 reported laboratory submissions
18 Uncertain significance · 1 Likely benign.
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. RAD51C, a DNA repair protein, is altered by mutation or deletion in certain breast cancers.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen RAD51C VCEP v1.0.0, with the data and sources behind each one.
27 criteria with recorded statuses: 2 met · 19 not met · 0 not assessed · 6 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_058216.3:c.431T>C (p.Ile144Thr) in RAD51C is a rare missense variant with extremely low population frequency (gnomAD v2.1 AF=0.0057%, v4.1 AF=0.014%). The ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Expert Panel has published RAD51C specifications (version 1.0.0) but no per-criterion rules were available for direct application; generic ACMG/AMP 2015 criteria were used as fallback.
The variant is absent or at extremely low frequency in population databases, meeting PM2 at supporting strength (gnomAD v4.1 overall AF=0.014%; 0 homozygotes). gnomAD v4.1 Middle Eastern subpopulation AF=0.279% is noted but remains below the BS1 threshold of 0.3%.
Myriad Genetics classified this variant as Likely benign (SCV004019909, criteria provided), meeting BP6 at supporting strength. However, the cited reference (PMID:25085752) is a BRCA1/BRCA2 reclassification algorithm and does not provide RAD51C-specific evidence.
In silico predictions are inconclusive: REVEL 0.314, BayesDel 0.041, SpliceAI delta 0.01, with Polyphen-2/SIFT suggesting possible damage but SNPs&GO predicting neutrality (PMID:23117857). Neither PP3 nor BP4 is met.
The variant has been observed in one Iraqi Jewish breast cancer proband (PMID:23117857) and one Danish HBOC family (PMID:26740214) but at insufficient frequency for PS4. No functional studies (PS3/BS3), segregation data (PP1/BS4), or de novo observations (PS2/PM6) are available.
The variant is not located in a statistically significant hotspot (PM1 not met), no alternative nucleotide changes at the same residue are established as pathogenic (PM5 not applicable), and RAD51C is not a gene with a low rate of benign missense variation (PP2 not met).
Overall classification: Uncertain significance. One supporting pathogenic criterion (PM2) is balanced by one supporting benign criterion (BP6), with all other criteria either not met or not applicable. This results in indeterminate classification under ACMG/AMP 2015 combination rules.
No criteria match.
Met · 2
PM2 SupportingNM_058216.3:c.431T>C is at extremely low frequency in population databases. gnomAD v2.1: AF=0.00566% (16/282,878 alleles, 0 homozygotes). gnomAD v4.1: AF=0.01419% (229/1,614,096 alleles, 0 homozygotes). Both overall frequencies are well below the 0.1% threshold. No homozygotes observed. Note: gnomAD v4.1 grpmax FAF=0.178% and Middle Eastern subpopulation AF=0.279%, which slightly moderates the strength but remains below the BS1 threshold of 0.3%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.00566% (16/282
- 878)
- gnomAD v4.1 AF=0.01419% (229/1
- 614
- 096)
- 0 homozygotes in both datasets.
Still missing
- Elevated frequency in gnomAD v4.1 Middle Eastern subpopulation (AF=0.279%) warrants monitoring as more population data accumulate.
Sources
BP6 SupportingMyriad Genetics, Inc. (SCV004019909) classified this variant as Likely benign with criteria provided. This represents a reputable clinical laboratory asserting a benign interpretation. While only a single submitter, it meets BP6 at supporting level. Details ▾Hide ▴
Evidence considered
- Myriad Genetics
- Inc. classified as Likely benign (SCV004019909
- criteria provided).
Still missing
- Myriad Genetics cited PMID:25085752 (BRCA1/BRCA2 reclassification algorithm
- not RAD51C-specific)
- the basis for the LB classification should be reviewed.
Sources
Not met · 19 · evaluated, threshold not reached
PS1 No evidence that the same amino acid change (p.Ile144Thr) has been established as pathogenic via a different nucleotide change. No alternative nucleotide substitutions at codon 144 were identified in ClinVar or the literature. Details ▾Hide ▴
Evidence considered
- No alternative nucleotide change leading to p.Ile144Thr identified.
Sources
clinvar ↗pm5_candidates
PS2 No de novo observation (maternity and paternity confirmed) has been reported for NM_058216.3:c.431T>C in any reviewed publication or ClinVar submission. Details ▾Hide ▴
Evidence considered
- No de novo data available.
Still missing
- No parental testing data available.
PS3 No variant-specific functional studies (e.g., HR assay, protein interaction, cellular sensitivity) have been reported for p.Ile144Thr in any reviewed publication. OncoKB did not identify any variant-specific reviewed functional evidence. Details ▾Hide ▴
Evidence considered
- No functional data available for this variant.
Still missing
- Functional characterization of p.Ile144Thr has not been performed.
Sources
PS4 The variant has been observed in affected individuals but at insufficient frequency and without controlled case-control comparison to reach statistical significance. One Iraqi Jewish proband with breast cancer (PMID:23117857; absent in 60 matched controls) and one Danish HBOC family (PMID:26740214). The aggregate data do not meet PS4 thresholds. Details ▾Hide ▴
Evidence considered
- Observed in 1/206 Jewish high-risk families (PMID:23117857)
- 1/1228 Danish HBOC families (PMID:26740214). No statistically significant enrichment versus controls.
Still missing
- Larger case-control studies needed to establish enrichment.
Sources
PM1 p.Ile144 is not located in a statistically significant mutational hotspot or a well-established critical functional domain for RAD51C. Hotspot analysis returned negative. Details ▾Hide ▴
Evidence considered
- Not in a statistically significant hotspot
- exact variant not listed in Cancer Hotspots.
PM6 No de novo observation with confirmed maternity and paternity has been reported for this variant. Details ▾Hide ▴
Evidence considered
- No de novo data available.
PP1 No segregation data available. The one family reported in PMID:23117857 (Iraqi Jewish proband with mother and sister affected) could not undergo co-segregation analysis because both relatives were deceased. Details ▾Hide ▴
Evidence considered
- Co-segregation analysis not possible — mother and sister deceased (PMID:23117857).
Still missing
- No informative segregation data.
Sources
PP2 RAD51C is not established as a gene with a low rate of benign missense variation. Both pathogenic and neutral missense variants are documented in the literature and ClinVar. Criterion not met. Details ▾Hide ▴
Evidence considered
- RAD51C has numerous reported missense variants of uncertain significance and benign classification.
Sources
PP3 In silico predictions are mixed and do not converge on a damaging effect. REVEL score 0.314 (below typical pathogenicity threshold of 0.5). BayesDel score 0.0405 (very low). SpliceAI max delta 0.01 (no splice impact). While Polyphen-2 and SIFT predicted possibly deleterious (PMID:23117857), SNPs&GO predicted neutral, and Align-GVGD gave C25 (borderline, PMID:26740214). The overall in silico profile does not support PP3. Details ▾Hide ▴
Evidence considered
- REVEL 0.314
- BayesDel 0.041
- SpliceAI delta 0.01
- Polyphen-2/SIFT possibly damaging but SNPs&GO neutral (PMID:23117857)
- Align-GVGD C25 borderline (PMID:26740214).
Sources
PP5 No reputable source (e.g., expert panel, clinical laboratory with multi-criteria review) has classified this variant as pathogenic or likely pathogenic. ClinVar reports it as Uncertain significance (18 labs). Details ▾Hide ▴
Evidence considered
- ClinVar classification: Uncertain significance (18 clinical laboratories). No expert panel asserting pathogenicity.
Sources
BA1 The variant is not common. Maximum subpopulation AF in gnomAD v4.1 is 0.279% (Middle Eastern), well below the 1% BA1 threshold. Overall AF across all populations is <0.015%. Details ▾Hide ▴
Evidence considered
- Highest subpopulation AF: 0.279% (gnomAD v4.1 Middle Eastern)
- overall AF: 0.014% (v4.1).
Sources
BS1 The variant does not exceed the 0.3% population frequency threshold. The highest subpopulation frequency is 0.279% in gnomAD v4.1 Middle Eastern, which is just below 0.3%. Overall AF is much lower (0.014%). Details ▾Hide ▴
Evidence considered
- Highest subpopulation AF: 0.279% (gnomAD v4.1 Middle Eastern) — below 0.3% BS1 threshold.
Sources
BS2 No homozygous individuals observed in gnomAD v2.1 (0/282,878) or gnomAD v4.1 (0/1,614,096). Absence of homozygotes does not provide evidence for a benign effect in an autosomal dominant disease gene where homozygosity is not expected in healthy populations. Details ▾Hide ▴
BS3 No functional studies have been reported demonstrating that p.Ile144Thr has no deleterious effect on protein function or splicing. Details ▾Hide ▴
Evidence considered
- No functional studies available for this variant.
Still missing
- Functional characterization not performed.
BS4 No segregation data available to demonstrate lack of co-segregation with disease. The one family reported (PMID:23117857) had affected relatives but co-segregation analysis was not possible. Details ▾Hide ▴
Evidence considered
- Co-segregation analysis not possible in the reported family (PMID:23117857).
Still missing
- No informative segregation data.
Sources
BP2 No data available on observation of this variant in trans with a known pathogenic RAD51C variant. Details ▾Hide ▴
Evidence considered
- No trans-configuration data available.
BP4 Multiple lines of in silico evidence are not consistently benign. REVEL 0.314 is below the typical pathogenic threshold but not clearly benign. BayesDel 0.0405 is very low and supportive of a benign interpretation. However, Polyphen-2 and SIFT predicted possibly deleterious (PMID:23117857). The overall computational evidence is mixed rather than consistently benign, and does not meet BP4. Details ▾Hide ▴
Evidence considered
- REVEL 0.314 (indeterminate)
- BayesDel 0.041 (low)
- Polyphen-2/SIFT possibly damaging (PMID:23117857)
- Align-GVGD C25 borderline (PMID:26740214).
Sources
BP5 No data available. This criterion requires the variant to be found in a case with an alternative molecular basis for disease, and no such information has been reported. Details ▾Hide ▴
Evidence considered
- No data on alternative molecular basis in variant carriers.
PS5 No data available. This criterion requires a variant to be identified as likely pathogenic by a reputable source without access to the primary data — not applicable here. Details ▾Hide ▴
No further detail was recorded.
Not applicable · 6· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_058216.3:c.431T>C is a missense variant (p.Ile144Thr) and does not fall into any null-variant category (nonsense, frameshift, canonical splice). Not eligible for PVS1 under generic ACMG/AMP or ClinGen SVI PVS1 framework. Details ▾Hide ▴
Evidence considered
- Missense substitution — not a predicted null variant.
Sources
pvs1_generic_framework ↗pvs1_variant_assessment
PM5 N/ANo pathogenic comparator variants at the same amino acid residue (Ile144) were identified. Automated PM5 candidate harvesting did not find any same-residue pathogenic missense changes. Details ▾Hide ▴
Evidence considered
- No same-residue pathogenic comparators in ClinVar.
Sources
pm5_candidates
PP4 N/ANo proband phenotype was provided for adjudication. PP4 requires the patient's phenotype or family history to be highly specific for the disease associated with RAD51C. Details ▾Hide ▴
Evidence considered
- No patient phenotype provided.
Still missing
- Proband phenotype and family history not available.
BP1 N/ARAD51C disease is not caused exclusively by truncating variants. Pathogenic missense variants in RAD51C are well documented (e.g., p.Gln143Arg, p.Arg258His), so BP1 does not apply. Details ▾Hide ▴
Evidence considered
- RAD51C has both pathogenic missense and truncating variants reported.
Sources
BP3 N/ASkipped by user instruction: trivially not_applicable (in-frame deletion/insertion in non-repetitive region; this is a missense substitution). Details ▾Hide ▴
No further detail was recorded.
BP7 N/ANM_058216.3:c.431T>C is a missense variant (p.Ile144Thr), not a synonymous variant. BP7 applies only to synonymous (silent) variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense substitution — BP7 not applicable.
Identifiers
- Gene
- RAD51C
- Transcript
- NM_058216.3
- Coding (HGVS c.)
- NM_058216.3:c.431T>C
- Protein (HGVS p.)
- NP_478123.1:p.(Ile144Thr)
- GRCh38
- chr17:58696719 T>C
- GRCh37
- chr17:56774080 T>C
- ClinVar
- 142840
Gene diagram
Every interpreted variant in RAD51C, mapped onto the exon structure of NM_058216.3. Select a row to find it on the plot.
RAD51CNM_058216.3
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in RAD51C
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
229 / 1,614,096 alleles
AF 0.000142 · 0 homozygotes · FAF 0.00178
gnomAD v2.1
16 / 282,878 alleles
AF 5.66e-05 · 0 homozygotes · FAF 0.000156
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.00014 · 229 / 1,614,096 alleles · 0 hom · FAF 0.0018
| Middle Eastern17 / 6,084 | 0.0028 |
| African/African American15 / 74,944 | 0.0002 |
| European (non-Finnish)186 / 1,180,046 | 0.00016 |
| Remaining individuals7 / 62,484 | 0.00011 |
| Admixed American3 / 60,004 | 5e-05 |
| South Asian1 / 91,090 | 1.1e-05 |
0 alternate alleles recorded in 4 other groups: European (Finnish), Amish, East Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 5.7e-05 · 16 / 282,878 alleles · 0 hom · FAF 0.00016
| African/African American6 / 24,968 | 0.00024 |
| European (non-Finnish)10 / 129,184 | 7.7e-05 |
0 alternate alleles recorded in 6 other groups: Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000141875; MAF= 0.01419%, 229/1614096 alleles, homozygotes = 0) and has highest observed frequency in the Middle Eastern population (AF= 0.00279421; MAF= 0.27942%, 17/6084 alleles, homozygotes = 0); grpmax FAF= 0.0017798.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 5.65615e-05; MAF= 0.00566%, 16/282878 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000240308; MAF= 0.02403%, 6/24968 alleles, homozygotes = 0); grpmax FAF= 0.00015629.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.314
- BayesDel
- 0.041
How the predictions were used
PP3 In silico predictions are mixed and do not converge on a damaging effect. REVEL score 0.314 (below typical pathogenicity threshold of 0.5). BayesDel score 0.0405 (very low). SpliceAI max delta 0.01 (no splice impact). While Polyphen-2 and SIFT predicted possibly deleterious (PMID:23117857), SNPs&GO predicted neutral, and Align-GVGD gave C25 (borderline, PMID:26740214). The overall in silico profile does not support PP3. Details ▾Hide ▴
Evidence considered
- REVEL 0.314
- BayesDel 0.041
- SpliceAI delta 0.01
- Polyphen-2/SIFT possibly damaging but SNPs&GO neutral (PMID:23117857)
- Align-GVGD C25 borderline (PMID:26740214).
Sources
BP4 Multiple lines of in silico evidence are not consistently benign. REVEL 0.314 is below the typical pathogenic threshold but not clearly benign. BayesDel 0.0405 is very low and supportive of a benign interpretation. However, Polyphen-2 and SIFT predicted possibly deleterious (PMID:23117857). The overall computational evidence is mixed rather than consistently benign, and does not meet BP4. Details ▾Hide ▴
Evidence considered
- REVEL 0.314 (indeterminate)
- BayesDel 0.041 (low)
- Polyphen-2/SIFT possibly damaging (PMID:23117857)
- Align-GVGD C25 borderline (PMID:26740214).
Sources
BP7 N/ANM_058216.3:c.431T>C is a missense variant (p.Ile144Thr), not a synonymous variant. BP7 applies only to synonymous (silent) variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense substitution — BP7 not applicable.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.314. BayesDel score = 0.0405109.
8 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Recorded publications
-
PMID 23117857 ↗Germline mutations in RAD51C in Jewish high cancer risk families.Kushnir A et al. · 2012RAD51C c.431T>C (p.Ile144Thr, rs28363307) identified in one Iraqi Jewish proband diagnosed with breast cancer at age 68 years. Mother and sister both diagnosed with breast cancer at ages 60 and 50 years, respectively; co-segregation analysis not possible as both were deceased. The variant was absent in 60 ethnically matched Iraqi cancer-free controls. In silico: Polyphen-2 and SIFT predicted possibly deleterious; SNPs&GO predicted neutral. The amino acid is evolutionarily conserved.Names this variant
Quoted passage
A p.431T>C alteration in exon 3 of the gene that results in altering Isoleucine to Threonine in codon 144 (p.Ile144Thr-rs28363307). The p.Ile144Thr mutation carrying proband was of Iraqi ancestry who was diagnosed with breast cancer at age 68 years.
Results, paragraph 2; Table 2 (line 389 in published table)
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PMID 25741868 ↗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.ACMG/AMP 2015 standards and guidelines for variant interpretation. Provides the generic framework used for criteria adjudication and classification combining rules. Does not mention any RAD51C variant.Does not name this variant
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PMID 26261251 ↗Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population.Song H et al. · 2015Case-control study of RAD51B/C/D mutations in 3,429 invasive EOC cases and 2,772 controls. Identified deleterious RAD51C mutations (14 in cases, 2 in controls) including truncating and splice variants plus one previously reported deleterious missense (c.428A>G, p.Gln143Arg). NM_058216.3:c.431T>C (p.Ile144Thr) was not specifically mentioned. Rare missense variants in RAD51C showed some association with ovarian cancer by burden testing.Does not name this variant
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PMID 26740214 ↗Identification of six pathogenic RAD51C mutations via mutational screening of 1228 Danish individuals with increased risk of hereditary breast and/or ovarian cancer.Jønson L et al. · 2016RAD51C c.431T>C (p.Ile144Thr, rs28363307) identified in one of 1228 Danish HBOC families. Classified as a variant of uncertain significance (VUS). ESP frequency 0.01%, absent from 2000 Danish exomes. Align-GVGD score C25 (borderline between neutral and deleterious). Interpreted as VUS by the authors.Names this variant
Quoted passage
c.431T>C, p.Ile144Thr, rs28363307, ESP 0.01%, 2000 Danish exomes: -, Align-GVGD: C25, Interpretation: VUS
Table 1, row for c.431T>C (line 337-343)
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PMID 36099300 ↗Homologous recombination-deficient mutation cluster in tumor suppressor RAD51C identified by comprehensive analysis of cancer variants.Comprehensive functional analysis of ~800 RAD51C missense variants of unknown significance using homology-directed recombination (HDR) assays. The abstract describes identification of an HR-deficient mutation cluster in RAD51C. Full text was not available for review; the abstract does not specifically mention p.Ile144Thr.Does not name this variant
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PMID 21537932 ↗A HRM-based screening method detects RAD51C germ-line deleterious mutations in Spanish breast and ovarian cancer families.Romero A et al. · 2011Describes RAD51C germline mutation screening by HRMA in 492 Spanish breast and/or ovarian cancer families. Identified 12 sequence variants including c.428A>G (p.Gln143Arg) but NM_058216.3:c.431T>C (p.Ile144Thr) was not identified in this cohort.Does not name this variant
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PMID 22538716 ↗Germline RAD51C mutations confer susceptibility to ovarian cancer.Loveday C et al. · 2012Reports 12 truncating RAD51C mutations in ovarian cancer families and discusses the role of RAD51C as an ovarian cancer susceptibility gene. NM_058216.3:c.431T>C (p.Ile144Thr) was not mentioned. Twelve nonsynonymous variants were identified but not individually listed in the main text; only c.790G>A (p.Gly264Ser) is referenced by name.Does not name this variant
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PMID 25186627 ↗Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel.Tung N et al. · 2015Reports frequency of germline mutations in 25 cancer susceptibility genes including RAD51C in 2158 individuals with breast cancer. The authors explicitly state no mutations were identified in RAD51C in either cohort. NM_058216.3:c.431T>C was not reported.Does not name this variant
Quoted passage
No mutations in either cohort were identified in the following genes: BMPR1A; CDK4; EPCAM; MLH1; PTEN, RAD51C, RAD51D; SMAD4; and STK11.
Results (line 311-316): 'No mutations in either cohort were identified in...RAD51C'
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
229 / 1,614,096 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.010
Open source ↗
ClinVar
18 Uncertain significance · 1 Likely benign
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1535377178
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/142840/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-56774080-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-58696719-T-C?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/17-58696719-T-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_058216.3%3Ac.431T…
- OncoKB ↗www.oncokb.org/gene/RAD51C/I144T
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=RAD51C+c.431T%3EC
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000141875; MAF= 0.01419%, 229/1614096 alleles, homozygotes = 0) and has highest observed frequency in the Middle Eastern population (AF= 0.00279421; MAF= 0.27942%, 17/6084 alleles, homozygotes = 0); grpmax FAF= 0.0017798.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 5.65615e-05; MAF= 0.00566%, 16/282878 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000240308; MAF= 0.02403%, 6/24968 alleles, homozygotes = 0); grpmax FAF= 0.00015629.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (18 clinical laboratories) and as Likely benign (1 clinical laboratory). (ClinVarID = 142840)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.314. BayesDel score = 0.0405109.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. RAD51C, a DNA repair protein, is altered by mutation or deletion in certain breast cancers.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.