About RAD51D
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
RAD51D c.26G>C, p.(Cys9Ser)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign classification under the recorded framework.
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 Not recorded. 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: 4
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
This variant is present in gnomAD at very low frequency: v2.1 AF = 0.0405% (113/278,930 alleles) and v4.1 AF = 0.0656% (1058/1,612,440 alleles), with grpmax FAF of 0.065% (v2.1) and 0.079% (v4.1), all below the 0.1% PM2 threshold for non-VCEP assessment. However, the presence of one homozygote in each database and over 100 observed alleles weakens the confidence; thus applied at supporting strength only.
Benign criteria applied · 4
BS2Supporting
BS2 · supporting
One homozygous individual is observed in gnomAD v2.1 and one homozygous individual is observed in gnomAD v4.1. RAD51D-associated cancer predisposition is adult-onset with moderate penetrance, so homozygous observation does not definitively exclude pathogenicity, but it provides supporting evidence that the variant can be tolerated in at least some individuals. Applied at supporting benign strength.
BP1Supporting
BP1 · supporting
RAD51D is a gene in which the primary disease mechanism is loss-of-function through truncating variants (nonsense, frameshift, canonical splice). The ACMG/AMP 2015 guidelines (PMID:25741868) specify BP1 for missense variants in genes where primarily truncating variants cause disease. The RAD51D locus is well-characterized as an ovarian cancer susceptibility gene where the vast majority of reported pathogenic variants are protein-truncating.
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence support a benign interpretation. REVEL score is 0.218 (benign-leaning, well below the 0.5 threshold). BayesDel score is 0.087 (low, consistent with benign). SpliceAI delta score is 0.00 (no predicted splicing impact). SIFT predicts tolerated (PMID:24130102). The aggregate in silico evidence indicates no significant impact on gene product.
BP6Supporting
BP6 · supporting
Nine clinical laboratories in ClinVar have classified this variant as Likely benign (variation ID 127886). Multiple reputable clinical testing laboratories independently arrived at a likely benign classification with criteria provided, including Ambry Genetics, LabCorp, and Quest Diagnostics. This represents a substantial body of clinical laboratory consensus favoring a benign interpretation.
Recorded classification: Likely benign
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BS2 supporting benign, BP1 supporting benign, BP4 supporting benign, BP6 supporting benign; combination = 1 supporting + 4 supporting benign, which maps to Likely Benign.
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
1,058 / 1,612,440 alleles
gnomAD v4.1: 1,058 / 1,612,440 alleles. Recorded AF 0.000656148. Recorded homozygote count 1.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00040512; MAF= 0.04051%, 113/278930 alleles, homozygotes = 1) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000718232; MAF= 0.07182%, 91/126700 alleles, homozygotes = 0); grpmax FAF= 0.00065141.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0011406844106463879, 21/18410 alleles, homozygotes = 0).
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
19 reported laboratory submissions
10 Uncertain significance · 9 Likely benign. ClinVar API review status: criteria provided, conflicting classifications.
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. RAD51D, a DNA repair protein, is infrequently altered in cancer.
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 Not recorded, with the data and sources behind each one.
29 criteria with recorded statuses: 5 met · 10 not met · 7 not assessed · 7 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_002878.3:c.26G>C (p.Cys9Ser) is a missense variant in exon 1 of RAD51D.
This variant is present in gnomAD at a low frequency: 0.0405% (113/278,930 alleles, 1 homozygote) in v2.1 and 0.0656% (1058/1,612,440 alleles, 1 homozygote) in v4.1, with a maximum population frequency of 0.083% in the European (non-Finnish) population (v4.1).
The variant has been reported in ClinVar (ID 127886) as Uncertain significance by 10 clinical laboratories and Likely benign by 9 clinical laboratories; no expert panel has reviewed this variant.
Multiple lines of computational evidence predict no significant impact on the gene product: REVEL score 0.218, BayesDel score 0.087, and SpliceAI maximum delta score 0.00.
PM2 (supporting) is applied because the variant is present at very low frequency in population databases (<0.1% AF in all populations), though weakened by the observation of homozygotes.
BP4 (supporting benign) is applied because multiple computational prediction algorithms (REVEL, BayesDel, SpliceAI) support no deleterious effect.
BP1 (supporting benign) is applied because RAD51D-associated disease is primarily caused by truncating loss-of-function variants rather than missense changes.
BS2 (supporting benign) is applied because one homozygous individual was observed in gnomAD v2.1 and one in gnomAD v4.1, suggesting this variant can be tolerated in at least some individuals.
BP6 (supporting benign) is applied because nine independent clinical laboratories have classified this variant as Likely benign with criteria provided.
PVS1 is not applicable as this is a missense variant, not a null variant.
PS3 is not met because no experimental functional studies have been performed for this variant.
PP3 is not met because the aggregate computational evidence supports a benign rather than pathogenic interpretation.
Using generic ACMG/AMP 2015 combination rules (PMID:25741868), the evidence profile includes: 1 supporting pathogenic criterion (PM2) and 4 supporting benign criteria (BP1, BP4, BS2, BP6). The net benign evidence outweighs the single pathogenic criterion, supporting a classification of Likely benign.
No criteria match.
Met · 5
PM2 SupportingThis variant is present in gnomAD at very low frequency: v2.1 AF = 0.0405% (113/278,930 alleles) and v4.1 AF = 0.0656% (1058/1,612,440 alleles), with grpmax FAF of 0.065% (v2.1) and 0.079% (v4.1), all below the 0.1% PM2 threshold for non-VCEP assessment. However, the presence of one homozygote in each database and over 100 observed alleles weakens the confidence; thus applied at supporting strength only. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF = 0.0405%
- grpmax FAF = 0.065%.
- gnomAD v4.1: AF = 0.0656%
- grpmax FAF = 0.079%.
Still missing
- One homozygote in each gnomAD version raises caution.
Sources
BS2 SupportingOne homozygous individual is observed in gnomAD v2.1 and one homozygous individual is observed in gnomAD v4.1. RAD51D-associated cancer predisposition is adult-onset with moderate penetrance, so homozygous observation does not definitively exclude pathogenicity, but it provides supporting evidence that the variant can be tolerated in at least some individuals. Applied at supporting benign strength. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 1 homozygote (exome).
- gnomAD v4.1: 1 homozygote.
Still missing
- Adult-onset disease with incomplete penetrance limits the strength of homozygous observations.
Sources
BP1 SupportingRAD51D is a gene in which the primary disease mechanism is loss-of-function through truncating variants (nonsense, frameshift, canonical splice). The ACMG/AMP 2015 guidelines (PMID:25741868) specify BP1 for missense variants in genes where primarily truncating variants cause disease. The RAD51D locus is well-characterized as an ovarian cancer susceptibility gene where the vast majority of reported pathogenic variants are protein-truncating. Details ▾Hide ▴
Evidence considered
- RAD51D disease mechanism is predominantly loss-of-function via truncating variants.
- ACMG/AMP 2015 BP1 rule applies to missense variants in LOF-predominant genes.
Sources
BP4 SupportingMultiple lines of computational evidence support a benign interpretation. REVEL score is 0.218 (benign-leaning, well below the 0.5 threshold). BayesDel score is 0.087 (low, consistent with benign). SpliceAI delta score is 0.00 (no predicted splicing impact). SIFT predicts tolerated (PMID:24130102). The aggregate in silico evidence indicates no significant impact on gene product. Details ▾Hide ▴
Evidence considered
- REVEL = 0.218.
- BayesDel = 0.087.
- SpliceAI max delta = 0.00.
- SIFT: tolerated (PMID:24130102).
Sources
BP6 SupportingNine clinical laboratories in ClinVar have classified this variant as Likely benign (variation ID 127886). Multiple reputable clinical testing laboratories independently arrived at a likely benign classification with criteria provided, including Ambry Genetics, LabCorp, and Quest Diagnostics. This represents a substantial body of clinical laboratory consensus favoring a benign interpretation. Details ▾Hide ▴
Evidence considered
- ClinVar ID 127886: 9 clinical laboratories report Likely benign.
- Multiple laboratories with criteria provided (Ambry Genetics SCV000185831
- LabCorp SCV000698094
- Quest SCV000602155).
Still missing
- No expert panel review
- classifications are single-submitter.
Sources
Not met · 10 · evaluated, threshold not reached
PS1 No evidence was identified that a different nucleotide change at codon 9 resulting in the same amino acid substitution (Cys9Ser) has been previously reported as pathogenic. The variant has been observed in population databases and reported as a variant of uncertain significance or likely benign in ClinVar. Details ▾Hide ▴
Evidence considered
- No alternative nucleotide change at c.26 resulting in p.Cys9Ser is reported as pathogenic in ClinVar or the literature.
Sources
PS3 No experimental functional studies have been performed for NM_002878.3:c.26G>C (p.Cys9Ser). OncoKB reports unknown oncogenic effect. One ovarian carcinoma with this variant showed loss of heterozygosity (PMID:22986143), but LOH is an observational tumor finding, not a functional assay demonstrating a deleterious effect. No variant-specific or systematic range functional characterization exists. Details ▾Hide ▴
Evidence considered
- OncoKB: unknown oncogenic effect
- no functional studies performed.
- PMID:22986143: tumor LOH observed but no in vitro functional assay was performed for p.C9S.
Still missing
- No functional studies available for this variant.
Sources
PS4 No case-control study demonstrates statistically significant enrichment of this variant in affected individuals compared to controls. The variant is present in gnomAD at ~0.04–0.07% frequency (113 alleles in v2.1; 1058 alleles in v4.1), which is incompatible with a highly penetrant rare pathogenic variant. One case and zero controls were reported in the Song et al. 2015 case-control study (PMID:26261251), insufficient for statistical significance. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 113/278
- 930 alleles (0.04%).
- gnomAD v4.1: 1058/1
- 612
- 440 alleles (0.066%).
- PMID:26261251: 1 case / 0 controls
- not significant.
Still missing
- No adequately powered case-control study specific to this variant.
Sources
PM1 Codon 9 (Cys9) lies in the N-terminal region of RAD51D, outside any established critical functional domain. Cancer Hotspots analysis confirms this position is not a statistically significant mutational hotspot. No literature establishes codon 9 as residing in a well-characterized functional domain whose disruption would satisfy PM1. Details ▾Hide ▴
Evidence considered
- Cancerhotspots.org: residue not significant.
- Position 9 is in the N-terminal region
- not within RAD51D's ATPase or DNA-binding domains.
Sources
PP2 RAD51D-associated disease is primarily driven by loss-of-function (truncating) variants. While rare missense variants can be pathogenic, the gene does not have a well-established low rate of benign missense variation that would satisfy PP2. Multiple common benign missense polymorphisms exist in RAD51D (e.g., p.Arg165Gln, p.Glu233Gly with MAF >1%), indicating a relatively high background of benign missense variation. Details ▾Hide ▴
Evidence considered
- RAD51D has several common missense polymorphisms (MAF >1%).
- Primary disease mechanism is loss-of-function through truncating variants.
Sources
PP3 Multiple lines of computational evidence predict no damaging effect. REVEL score is 0.218 (well below the 0.5 threshold for pathogenicity). BayesDel score is 0.087 (low). SpliceAI maximum delta score is 0.00, indicating no predicted splicing impact. The aggregate in silico evidence is consistent with a benign interpretation, not supporting PP3. Details ▾Hide ▴
Evidence considered
- REVEL = 0.218 (benign-leaning).
- BayesDel = 0.087 (low).
- SpliceAI max delta = 0.00 (no splicing impact).
Sources
PP5 No reputable source has classified this variant as pathogenic. ClinVar reports this variant as Uncertain significance (10 clinical laboratories) and Likely benign (9 clinical laboratories) under variation ID 127886. No expert panel has asserted pathogenicity. Details ▾Hide ▴
Evidence considered
- ClinVar ID 127886: VUS (10 labs)
- Likely benign (9 labs)
- no expert panel review.
- No reputable source reports this variant as pathogenic.
Sources
BA1 The maximum observed allele frequency in gnomAD is 0.083% (v4.1 NFE), well below the 1% BA1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 max AF (NFE) = 0.072%.
- gnomAD v4.1 max AF (NFE) = 0.083%.
Sources
BS1 The maximum observed allele frequency in gnomAD is 0.083% (v4.1 NFE), below the 0.3% BS1 threshold for non-VCEP assessment. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 max AF (NFE) = 0.072%.
- gnomAD v4.1 max AF (NFE) = 0.083%.
Sources
BS3 No in vitro or in vivo functional studies have been performed to evaluate the effect of p.Cys9Ser on RAD51D protein function. The absence of functional data does not satisfy BS3, which requires positive evidence of no damaging effect from well-established functional assays. Details ▾Hide ▴
Evidence considered
- OncoKB: unknown oncogenic effect
- functional studies have not been performed.
Still missing
- No functional studies available.
Sources
Not assessed · 7 · no assessment recorded
PS2 No de novo data are available for this variant. Paternity and maternity were not confirmed. Details ▾Hide ▴
Still missing
- No de novo testing data available.
PM6 No de novo data are available for this variant. No specific de novo report was identified in the literature. Details ▾Hide ▴
Still missing
- No de novo testing data available.
PP1 No co-segregation data are available for this variant. Details ▾Hide ▴
Still missing
- No family-based co-segregation data available.
PP4 No proband phenotype or clinical history was provided for the index case. Variant-level phenotype specificity cannot be evaluated without patient-level data. Details ▾Hide ▴
Still missing
- Patient phenotype and clinical history not available.
BS4 No co-segregation data are available to evaluate lack of segregation with disease in affected families. Details ▾Hide ▴
Still missing
- No family-based segregation data available.
BP2 No data are available regarding observation of this variant in trans with a known pathogenic variant in RAD51D. Details ▾Hide ▴
Still missing
- No phasing data with pathogenic RAD51D variants available.
BP5 No data are available regarding an alternate molecular basis for disease in a proband carrying this variant. Details ▾Hide ▴
Still missing
- No clinical data on alternate molecular diagnoses in carriers.
Not applicable · 7· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_002878.3:c.26G>C is a missense variant (p.Cys9Ser) located in exon 1; it does not fall into the null-variant buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants required for PVS1 under the ClinGen SVI PVS1 framework (PMC6185798). Details ▾Hide ▴
Evidence considered
- Missense substitution at c.26G>C
- variant bucket 'other' in generic PVS1 decision tree.
Sources
pvs1_generic_framework ↗pvs1_variant_assessment
PM3 N/APM3 was specified as trivially not applicable. RAD51D-associated disease displays autosomal dominant inheritance; there is no evidence for a recessive mode of inheritance. No data on trans observations are available. Details ▾Hide ▴
No further detail was recorded.
PM4 N/APM4 was specified as trivially not applicable. This is a substitution variant, not a protein length-altering variant (in-frame deletion/insertion or stop-loss). Details ▾Hide ▴
No further detail was recorded.
PM5 N/ANo same-residue comparator variants at codon 9 with a different missense change classified as pathogenic were identified in automated PM5 candidate harvesting. Manual review also found no evidence of pathogenic variants at this position in ClinVar or the literature. Details ▾Hide ▴
Evidence considered
- Automated PM5 search returned zero same-residue pathogenic candidates.
Sources
pm5_candidates
BP3 N/ABP3 was specified as trivially not applicable (in-frame deletion/insertion in non-repetitive region). This is a substitution variant. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ANM_002878.3:c.26G>C is a missense variant (p.Cys9Ser), not a synonymous or intronic variant. BP7 applies to synonymous variants for which splicing prediction algorithms predict no impact, not to missense substitutions. Details ▾Hide ▴
No further detail was recorded.
PS5 N/APS5 is not a standard ACMG/AMP 2015 criterion. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- RAD51D
- Transcript
- NM_002878.3
- Coding (HGVS c.)
- NM_002878.3:c.26G>C
- Protein (HGVS p.)
- NP_002869.3:p.(Cys9Ser)
- GRCh38
- chr17:35119588 C>G
- GRCh37
- chr17:33446607 C>G
- ClinVar
- 127886
Gene diagram
Every interpreted variant in RAD51D, mapped onto the exon structure of NM_002878.3. Select a row to find it on the plot.
RAD51DNM_002878.3
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 RAD51D
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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
1,058 / 1,612,440 alleles
AF 0.000656 · 1 homozygotes · FAF 0.000787
gnomAD v2.1
113 / 278,930 alleles
AF 0.000405 · 1 homozygotes · FAF 0.000651
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.00066 · 1058 / 1,612,440 alleles · 1 hom · FAF 0.00079
| European (non-Finnish)980 / 1,179,946 | 0.00083 |
| Remaining individuals49 / 62,474 | 0.00078 |
| Admixed American15 / 60,030 | 0.000251 hom |
| African/African American12 / 75,044 | 0.00016 |
| European (Finnish)2 / 62,412 | 3.2e-05 |
0 alternate alleles recorded in 5 other groups: Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 0.00041 · 113 / 278,930 alleles · 1 hom · FAF 0.00065
| European (non-Finnish)91 / 126,700 | 0.00072 |
| Remaining individuals3 / 7,184 | 0.00042 |
| Admixed American13 / 35,410 | 0.000371 hom |
| African/African American5 / 24,874 | 0.0002 |
| European (Finnish)1 / 23,926 | 4.2e-05 |
0 alternate alleles recorded in 3 other groups: Ashkenazi Jewish, East Asian, South Asian.
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000656148; MAF= 0.06561%, 1058/1612440 alleles, homozygotes = 1) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000830546; MAF= 0.08305%, 980/1179946 alleles, homozygotes = 0); grpmax FAF= 0.00078695.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00040512; MAF= 0.04051%, 113/278930 alleles, homozygotes = 1) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000718232; MAF= 0.07182%, 91/126700 alleles, homozygotes = 0); grpmax FAF= 0.00065141.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0011406844106463879, 21/18410 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.218
- BayesDel
- 0.087
How the predictions were used
BP4 SupportingMultiple lines of computational evidence support a benign interpretation. REVEL score is 0.218 (benign-leaning, well below the 0.5 threshold). BayesDel score is 0.087 (low, consistent with benign). SpliceAI delta score is 0.00 (no predicted splicing impact). SIFT predicts tolerated (PMID:24130102). The aggregate in silico evidence indicates no significant impact on gene product. Details ▾Hide ▴
Evidence considered
- REVEL = 0.218.
- BayesDel = 0.087.
- SpliceAI max delta = 0.00.
- SIFT: tolerated (PMID:24130102).
Sources
PP3 Multiple lines of computational evidence predict no damaging effect. REVEL score is 0.218 (well below the 0.5 threshold for pathogenicity). BayesDel score is 0.087 (low). SpliceAI maximum delta score is 0.00, indicating no predicted splicing impact. The aggregate in silico evidence is consistent with a benign interpretation, not supporting PP3. Details ▾Hide ▴
Evidence considered
- REVEL = 0.218 (benign-leaning).
- BayesDel = 0.087 (low).
- SpliceAI max delta = 0.00 (no splicing impact).
Sources
BP7 N/ANM_002878.3:c.26G>C is a missense variant (p.Cys9Ser), not a synonymous or intronic variant. BP7 applies to synonymous variants for which splicing prediction algorithms predict no impact, not to missense substitutions. Details ▾Hide ▴
No further detail was recorded.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.218. BayesDel score = 0.0874681.
8 paper records listed. 1 cited in the classification.
Cited in the classification
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PMID 24130102 ↗About 1% of the breast and ovarian Spanish families testing negative for BRCA1 and BRCA2 are carriers of RAD51D pathogenic variants.Screened 842 Spanish BC/OC families for RAD51D mutations. c.26G>C (p.Cys9Ser, rs140825795) was identified as a nonsynonymous variant in 1/842 index cases (MAF 0.0006). In silico predictions: SIFT tolerated, PolyPhen possibly damaging, Condel deleterious, no splicing effect. Not considered pathogenic by the authors; listed separately from the three clearly pathogenic/likely pathogenic mutations identified.→ BP4 Names this variant
Source detail
c.26G>C p.Cys9Ser rs140825795 C0 Tolerated Possibly damaging Deleterious No effect 0.0006 (842)
Location Table 1 (Nonsynonymous variants section)
Other recorded publications
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PMID 21822267 ↗Germline mutations in RAD51D confer susceptibility to ovarian cancer.Loveday C et al. · 2011Identified eight inactivating RAD51D mutations in breast-ovarian cancer families, establishing RAD51D as an ovarian cancer susceptibility gene. NM_002878.3:c.26G>C was not mentioned in this paper.Does not name this variant
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PMID 22986143 ↗Loss of function germline mutations in RAD51D in women with ovarian carcinoma.Wickramanayake A et al. · 2012Identified p.C9S as one of five rare RAD51D missense variants in a cohort of 360 ovarian carcinoma patients. One tumor with p.C9S showed loss of the wildtype allele, but the variant occurred at similar frequency in European American controls and was predicted to be benign by SIFT.Names this variant
Quoted passage
One of five neoplasms with a missense variant (p.C9S) revealed loss of the wildtype allele, but this variant occurred at similar frequency in European American controls and was predicted by SIFT to be benign.
Results section; Table 2
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PMID 24139550 ↗Germline mutation in the RAD51B gene confers predisposition to breast cancer.Golmard L et al. · 2013Analyzed RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3) for germline mutations conferring breast cancer predisposition. NM_002878.3:c.26G>C was not mentioned.Does not name this variant
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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 interpretation of sequence variants. Provides the classification framework used in this assessment. NM_002878.3:c.26G>C was not mentioned.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. · 2015Sequenced RAD51B, RAD51C, and RAD51D in 3,429 ovarian cancer cases and 2,772 controls. C9S (c.26G>C) was identified in 1 case and 0 controls among missense variants with MAF <1%, but was not among the deleterious mutation category. RAML burden test for RAD51D missense variants showed some evidence of association with serous ovarian cancer (P=0.012).Names this variant
Quoted passage
RAD51D 17 33446607 26G>C Exon 1 C9S 1 0 1 2 2 5
Appendix Table A4
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PMID 28135145 ↗Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.Yurgelun MB et al. · 2017Performed germline testing of 25 cancer susceptibility genes in 1,058 colorectal cancer patients. c.26G>C (p.Cys9Ser) was listed as a variant of uncertain significance in RAD51D, identified in one participant. It was not among the pathogenic or likely pathogenic mutations reported.Names this variant
Quoted passage
RAD51D c.26G>C (p.Cys9Ser)
Appendix Table A4 (VUS listing)
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PMID 33203166 ↗Outcome of Targeted Therapy Recommendations for Metastatic and Recurrent Head and Neck Cancers.Study of targeted therapy outcomes in head and neck cancers. Abstract and available metadata do not mention RAD51D or NM_002878.3:c.26G>C. No full text or abstract content relevant to this variant was identified.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
1,058 / 1,612,440 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
10 Uncertain significance · 9 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 ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/127886/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-33446607-C-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-35119588-C-G?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/17-35119588-C-G
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_002878.3%3Ac.26G%…
- OncoKB ↗www.oncokb.org/gene/RAD51D/C9S
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=RAD51D+c.26G%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= 0.000656148; MAF= 0.06561%, 1058/1612440 alleles, homozygotes = 1) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000830546; MAF= 0.08305%, 980/1179946 alleles, homozygotes = 0); grpmax FAF= 0.00078695.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00040512; MAF= 0.04051%, 113/278930 alleles, homozygotes = 1) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000718232; MAF= 0.07182%, 91/126700 alleles, homozygotes = 0); grpmax FAF= 0.00065141.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0011406844106463879, 21/18410 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Uncertain significance (10 clinical laboratories) and as Likely benign (9 clinical laboratories). (ClinVarID = 127886)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.218. BayesDel score = 0.0874681.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. RAD51D, a DNA repair protein, is infrequently altered in cancer.
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.