About RAD51D
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
RAD51D c.422T>C, p.(Leu141Pro)
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 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: 0
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
NM_002878.3:c.422T>C is present at extremely low frequency in population databases: gnomAD v2.1 AF=3.98e-06 (1/251,470 alleles, 0.0004%) and gnomAD v4.1 AF=1.12e-05 (18/1,614,128 alleles, 0.0011%). Both are well below the 0.1% threshold for PM2. Absent from gnomAD-Canada v1.0.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
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; combination = 1 supporting, 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
18 / 1,614,128 alleles
gnomAD v4.1: 18 / 1,614,128 alleles. Recorded AF 1.11515e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.97662e-06; MAF= 0.00040%, 1/251470 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.79152e-06; MAF= 0.00088%, 1/113746 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.040 maximum delta
Recorded SpliceAI maximum delta score: 0.040. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
7 reported laboratory submissions
7 Uncertain significance.
Context only
ClinVar ↗
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: 1 met · 9 not met · 11 not assessed · 8 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.422T>C (p.Leu141Pro) is a missense variant in RAD51D, a moderate-penetrance ovarian cancer predisposition gene where loss-of-function is the established disease mechanism.
This variant is present at extremely low frequency in population databases: gnomAD v2.1 AF=0.0004% (1/251,470 alleles) and gnomAD v4.1 AF=0.0011% (18/1,614,128 alleles), and is absent from gnomAD-Canada. PM2 (supporting) is met.
ClinVar reports this variant as Uncertain significance by seven clinical laboratories with review status 'criteria provided, single submitter.' No expert panel pathogenic or benign classification exists.
In silico predictions are mixed: REVEL score 0.44 (indeterminate), BayesDel score 0.07 (benign), and SpliceAI max delta 0.04 (no splice impact). These do not meet PP3 or BP4 thresholds.
No functional studies, case-control data, cosegregation data, or de novo observations are available for this variant. PS3, PS4, PP1, PS2, and PM6 remain unassessed.
No same-residue pathogenic comparator exists at Leu141, precluding PS1 and PM5 application.
RAD51D has both established pathogenic truncating and missense variants; BP1 is not met because missense variants cannot be presumed benign in this gene.
Overall, this variant meets only PM2 (supporting). All other applicable criteria are either not met or cannot be assessed due to insufficient evidence. The variant remains of uncertain significance.
No criteria match.
Met · 1
PM2 SupportingNM_002878.3:c.422T>C is present at extremely low frequency in population databases: gnomAD v2.1 AF=3.98e-06 (1/251,470 alleles, 0.0004%) and gnomAD v4.1 AF=1.12e-05 (18/1,614,128 alleles, 0.0011%). Both are well below the 0.1% threshold for PM2. Absent from gnomAD-Canada v1.0. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 1/251
- 470 alleles (AF=0.0004%)
- gnomAD v4.1: 18/1
- 614
- 128 alleles (AF=0.0011%
- grpmax FAF=9.53e-06)
- gnomAD-Canada: absent (0 alleles)
Sources
Not met · 9 · evaluated, threshold not reached
PM1 Leu141 does not lie in a statistically significant mutational hotspot in RAD51D. No evidence supports that this residue falls within a well-established functional domain without benign variation. Details ▾Hide ▴
Evidence considered
- Hotspots analysis: residue_significant=false
- exact_variant_listed=no
- residue is not in a recognized hotspot
Still missing
- Domain-specific constraint data could refine this assessment
PP2 PP2 requires a gene where missense variants are a common mechanism of disease AND the gene has a low rate of benign missense variation. In RAD51D, the primary disease mechanism is loss-of-function through truncating variants; missense variants can be pathogenic but are not the predominant mechanism. This criterion is not met. Details ▾Hide ▴
Evidence considered
- RAD51D disease mechanism is primarily LoF/truncating
- missense is not the common mechanism
PP3 In silico predictions are mixed and do not consistently support a deleterious effect. REVEL score is 0.44 (indeterminate, below the 0.5 pathogenic threshold). BayesDel score is 0.07 (benign range). SpliceAI max delta is 0.04 (no predicted splice impact). Multiple lines of computational evidence do NOT converge on a deleterious prediction. Details ▾Hide ▴
Evidence considered
- REVEL: 0.44 (indeterminate
- threshold for pathogenic typically ≥0.5)
- BayesDel: 0.07 (benign
- threshold for pathogenic typically ≥0.27)
- SpliceAI: max delta 0.04 (no splice impact)
Still missing
- HCI Prior not available for RAD51D
Sources
PP5 No reputable source has recently reported NM_002878.3:c.422T>C as pathogenic. ClinVar reports this variant as Uncertain significance from seven clinical laboratories, with review status 'criteria provided, single submitter.' No expert panel classification is available. Details ▾Hide ▴
Evidence considered
- ClinVar: Uncertain significance (7 submitters)
- no expert panel or multi-submitter pathogenic consensus
Sources
BA1 gnomAD v4.1 allele frequency is 0.0011% (1.12e-05), well below the 1% threshold for BA1. The variant is not common in any population. Details ▾Hide ▴
BS1 gnomAD v4.1 allele frequency is 0.0011%, well below the 0.3% threshold for BS1. The variant is not observed at a frequency greater than expected for the disorder. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF=0.0004%
- gnomAD v4.1: AF=0.0011% (grpmax FAF=9.53e-06)
Sources
BP1 BP1 applies to missense variants in genes where primarily truncating variants cause disease. While RAD51D loss-of-function is an established disease mechanism, pathogenic missense variants in RAD51D are also well-documented (e.g., in the ACMG clinical practice resource PMID:41070818). Missense variants at this gene cannot be presumed benign solely because truncating variants are pathogenic. Details ▾Hide ▴
Evidence considered
- RAD51D has both truncating and missense pathogenic variants
- BP1 presumption does not hold
Sources
pvs1_gene_context
BP4 Computational evidence does not consistently suggest no impact. BayesDel score of 0.07 supports a benign interpretation, but REVEL score of 0.44 falls in the indeterminate range (neither clearly benign nor pathogenic). SpliceAI shows no splicing effect (max delta 0.04). The mixed signal does not satisfy the requirement for multiple lines of computational evidence converging on no impact. Details ▾Hide ▴
Evidence considered
- BayesDel: 0.07 (benign)
- REVEL: 0.44 (indeterminate
- below 0.5 but not clearly benign)
- SpliceAI: max delta 0.04 (no splice impact)
Sources
BP6 No reputable source has recently reported NM_002878.3:c.422T>C as benign. ClinVar classification is Uncertain significance. BP6 requires a reputable source reporting the variant as benign without access to primary data for independent evaluation. Details ▾Hide ▴
Evidence considered
- ClinVar: Uncertain significance from 7 submitters
- no benign classification from any reputable source
Sources
Not assessed · 11 · no assessment recorded
PS1 No known pathogenic variant with a different amino acid change at the same residue (Leu141) was identified. PM5 candidate search found zero same-residue comparator variants in ClinVar. PS1 cannot be applied without evidence of a different pathogenic missense change at this position. Details ▾Hide ▴
Evidence considered
- pm5_candidates.json returned zero same-residue candidates
- unable to identify a known pathogenic alternate change at Leu141
Still missing
- No same-residue comparator variants at Leu141 in ClinVar or literature
Sources
pm5_candidates
PS2 No de novo data available for NM_002878.3:c.422T>C. None of the reviewed publications or ClinVar submissions report de novo occurrence of this variant. Details ▾Hide ▴
Evidence considered
- No de novo observation reported in ClinVar submissions or literature
Still missing
- No de novo testing data available for this variant
PS3 No variant-specific functional studies identified. OncoKB reports unknown oncogenic effect for this variant. Literature review found no functional characterization of NM_002878.3:c.422T>C (p.Leu141Pro) in any experimental system. Details ▾Hide ▴
Evidence considered
- OncoKB classification: Unknown Oncogenic Effect
- no functional PMIDs identified for this variant
Still missing
- No functional assay data available for p.Leu141Pro
- DNA repair functional studies recommended
Sources
PS4 No case-control or cohort studies comparing the prevalence of NM_002878.3:c.422T>C in affected vs. unaffected individuals were identified. The variant has been observed in clinical testing and reported as VUS by seven laboratories, but no statistically enriched case series or odds-ratio data are available. Details ▾Hide ▴
Evidence considered
- ClinVar: 7 clinical laboratories report VUS
- no case-control enrichment data
Still missing
- No case-control or cohort enrichment data for this variant
Sources
PM6 No de novo data available. PM6 requires confirmation of de novo occurrence with confirmed maternity and paternity; no such evidence was identified for this variant in any reviewed source. Details ▾Hide ▴
Evidence considered
- No de novo reports in ClinVar submissions or reviewed literature
Still missing
- No de novo testing data
PP1 No cosegregation data available. PP1 requires demonstration of variant cosegregation with disease in multiple affected family members; no family studies were identified for this variant. Details ▾Hide ▴
Evidence considered
- No cosegregation data in ClinVar submissions or literature
Still missing
- No family segregation studies available
PP4 No patient phenotype or family history data are available to assess whether the clinical presentation is highly specific for RAD51D-associated disease. Details ▾Hide ▴
Evidence considered
- No proband phenotype or family history data in case materials
Still missing
- Patient phenotype and family history data not available for adjudication
BS2 No data on observation of this variant in healthy adults where full penetrance would be expected at an early age. BS2 requires observation in controls where disease would have manifested if the variant were pathogenic. Details ▾Hide ▴
Evidence considered
- No healthy adult observation data with full-penetrance expectation
Still missing
- No observation data in healthy adult controls with expected full penetrance
BS3 No functional studies have been performed on NM_002878.3:c.422T>C (p.Leu141Pro) that demonstrate no damaging effect on protein function or splicing. Details ▾Hide ▴
Evidence considered
- No variant-specific functional assays identified in literature or databases
Still missing
- Functional characterization of p.Leu141Pro in DNA repair assays would inform this criterion
BS4 No cosegregation data demonstrating lack of segregation with disease are available for this variant. Details ▾Hide ▴
Evidence considered
- No family studies showing lack of segregation with disease
Still missing
- No segregation analysis data available
BP2 No data on observation of this variant in trans with a pathogenic variant for a fully penetrant dominant disorder, or in cis with a pathogenic variant. No phasing data are available. Details ▾Hide ▴
Evidence considered
- No trans/cis configuration data available
Still missing
- Phasing data not available
Not applicable · 8· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_002878.3:c.422T>C is a missense substitution (p.Leu141Pro). This variant does not fall into the null-variant buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants required for PVS1 application per the ClinGen SVI PVS1 framework (PMC6185798). PVS1 is not applicable to missense variants. Details ▾Hide ▴
Evidence considered
- Missense substitution at c.422T>C
- variant_bucket='other'
- apply_generic_pvs1_framework=false per automated PVS1 assessment
Sources
pvs1_generic_framework ↗pvs1_variant_assessment
PM3 N/APM3 applies to recessive disorders where the variant is detected in trans with a pathogenic variant. RAD51D-associated cancer predisposition is not a recessive disorder in this context. Details ▾Hide ▴
Evidence considered
- Not a recessive disorder context for RAD51D germline cancer predisposition
PM4 N/ANM_002878.3:c.422T>C is a single-nucleotide substitution, not an in-frame deletion/insertion or stop-loss variant. PM4 applies only to non-repeat region protein length changes. Details ▾Hide ▴
Evidence considered
- Variant is a substitution
- not a protein length-altering variant
PM5 N/ANo same-residue comparator variants at Leu141 were identified in ClinVar. PM5 requires a different pathogenic missense change at the same amino acid position; automated candidate harvesting found zero eligible comparators. Details ▾Hide ▴
Evidence considered
- pm5_candidates.json: 0 same-residue candidates
- 0 expert-panel PLP candidates
- recommendation=not_applicable
Still missing
- No pathogenic comparator at Leu141 in current ClinVar data
Sources
pm5_candidates
BP3 N/ANM_002878.3:c.422T>C is a single-nucleotide substitution, not an in-frame insertion/deletion or stop-loss variant. BP3 applies only to in-frame indels in repetitive regions without a known function. Details ▾Hide ▴
Evidence considered
- Variant is a substitution
- not an in-frame indel
BP5 N/ABP5 applies when a variant is observed in a case with an alternate molecular basis for disease. No such observation exists for this variant; the criterion is not applicable in the absence of an alternate molecular diagnosis. Details ▾Hide ▴
Evidence considered
- No case with alternate molecular basis identified
BP7 N/ANM_002878.3:c.422T>C is a missense variant (p.Leu141Pro), not a synonymous/silent variant. BP7 specifically applies to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense substitution
- not synonymous
PS5 N/APS5 applies to variants found in trans with a pathogenic variant for recessive disorders. RAD51D-associated cancer predisposition is not a recessive disorder in this context, and no trans configuration data exist for this variant. Details ▾Hide ▴
Evidence considered
- Not a recessive disorder context for RAD51D germline cancer predisposition
Identifiers
- Gene
- RAD51D
- Transcript
- NM_002878.3
- Coding (HGVS c.)
- NM_002878.3:c.422T>C
- Protein (HGVS p.)
- NP_002869.3:p.(Leu141Pro)
- GRCh38
- chr17:35107046 A>G
- GRCh37
- chr17:33434065 A>G
- ClinVar
- 186683
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
18 / 1,614,128 alleles
AF 1.12e-05 · 0 homozygotes · FAF 9.53e-06
gnomAD v2.1
1 / 251,470 alleles
AF 3.98e-06 · 0 homozygotes
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.1e-05 · 18 / 1,614,128 alleles · 0 hom · FAF 9.5e-06
| European (non-Finnish)18 / 1,180,018 | 1.5e-05 |
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 4e-06 · 1 / 251,470 alleles · 0 hom
| European (non-Finnish)1 / 113,746 | 8.8e-06 |
0 alternate alleles recorded in 7 other groups: African/African American, 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= 1.11515e-05; MAF= 0.00112%, 18/1614128 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.5254e-05; MAF= 0.00153%, 18/1180018 alleles, homozygotes = 0); grpmax FAF= 9.53e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.97662e-06; MAF= 0.00040%, 1/251470 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.79152e-06; MAF= 0.00088%, 1/113746 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.440
- BayesDel
- 0.070
How the predictions were used
PP3 In silico predictions are mixed and do not consistently support a deleterious effect. REVEL score is 0.44 (indeterminate, below the 0.5 pathogenic threshold). BayesDel score is 0.07 (benign range). SpliceAI max delta is 0.04 (no predicted splice impact). Multiple lines of computational evidence do NOT converge on a deleterious prediction. Details ▾Hide ▴
Evidence considered
- REVEL: 0.44 (indeterminate
- threshold for pathogenic typically ≥0.5)
- BayesDel: 0.07 (benign
- threshold for pathogenic typically ≥0.27)
- SpliceAI: max delta 0.04 (no splice impact)
Still missing
- HCI Prior not available for RAD51D
Sources
BP4 Computational evidence does not consistently suggest no impact. BayesDel score of 0.07 supports a benign interpretation, but REVEL score of 0.44 falls in the indeterminate range (neither clearly benign nor pathogenic). SpliceAI shows no splicing effect (max delta 0.04). The mixed signal does not satisfy the requirement for multiple lines of computational evidence converging on no impact. Details ▾Hide ▴
Evidence considered
- BayesDel: 0.07 (benign)
- REVEL: 0.44 (indeterminate
- below 0.5 but not clearly benign)
- SpliceAI: max delta 0.04 (no splice impact)
Sources
BP7 N/ANM_002878.3:c.422T>C is a missense variant (p.Leu141Pro), not a synonymous/silent variant. BP7 specifically applies to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense substitution
- not synonymous
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.04). REVEL score = 0.44. BayesDel score = 0.0702953.
7 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
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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 consensus guidelines for the interpretation of sequence variants. Provides the framework used for this adjudication but does not discuss NM_002878.3:c.422T>C or any specific RAD51D variants.Does not name this variant
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PMID 34326862 ↗Analysis of Sequence and Copy Number Variants in Canadian Patient Cohort With Familial Cancer Syndromes Using a Unique Next Generation Sequencing Based Approach.Bhai P et al. · 2021Analysis of sequence and copy number variants in Canadian familial cancer patients using NGS panel testing. The abstract describes a general approach to hereditary cancer testing but does not mention NM_002878.3:c.422T>C or any specific RAD51D variants.Does not name this variant
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PMID 18163131 ↗The emerging landscape of breast cancer susceptibility.Stratton MR et al. · 2008Review of the emerging landscape of breast cancer susceptibility alleles, discussing high-penetrance, moderate-penetrance, and low-penetrance classes. Provides gene-level context for breast cancer predisposition but does not discuss RAD51D or NM_002878.3:c.422T>C specifically.Does not name this variant
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PMID 19305347 ↗ACOG Practice Bulletin No. 103: Hereditary breast and ovarian cancer syndrome.2009ACOG Practice Bulletin No. 103 on hereditary breast and ovarian cancer syndrome, providing clinical management guidelines. Discusses BRCA1/BRCA2 testing and management but does not mention RAD51D or NM_002878.3:c.422T>C.Does not name this variant
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PMID 23188549 ↗NSGC practice guideline: risk assessment and genetic counseling for hereditary breast and ovarian cancer.NSGC practice guideline for risk assessment and genetic counseling for hereditary breast and ovarian cancer. Focuses on BRCA1/BRCA2 counseling approaches; does not discuss RAD51D or NM_002878.3:c.422T>C.Does not name this variant
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PMID 25356965 ↗ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing.ACMG policy statement on updated recommendations for analysis and reporting of secondary findings in clinical genome-scale sequencing. Discusses general reporting frameworks; does not mention RAD51D or NM_002878.3:c.422T>C.Does not name this variant
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PMID 26389258 ↗Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional VersiPDQ Cancer Genetics Risk Assessment and Counseling summary. No abstract available; the topic is general cancer genetics risk assessment and does not address specific RAD51D variants.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
18 / 1,614,128 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.040
Open source ↗
ClinVar
7 Uncertain significance
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/186683/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-33434065-A-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-35107046-A-G?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/17-35107046-A-G
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_002878.3%3Ac.422T…
- OncoKB ↗www.oncokb.org/gene/RAD51D/L141P
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=RAD51D+c.422T%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= 1.11515e-05; MAF= 0.00112%, 18/1614128 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.5254e-05; MAF= 0.00153%, 18/1180018 alleles, homozygotes = 0); grpmax FAF= 9.53e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.97662e-06; MAF= 0.00040%, 1/251470 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.79152e-06; MAF= 0.00088%, 1/113746 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (7 clinical laboratories). (ClinVarID = 186683)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.04). REVEL score = 0.44. BayesDel score = 0.0702953.
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.