RAD51B c.171_173dup, p.(Ser57dup)

Reasoning

PM2 is met at supporting strength based on rarity in large reference populations. The variant is present only once in gnomAD v4.1 (total AF 6.20005e-07; 1/1,612,890 alleles), once in gnomAD v2.1 (AF 3.98597e-06; 1/250,880 alleles), and is absent from gnomAD-Canada v1.0. The highest displayed subpopulation frequencies remain very rare (4.31704e-05 in gnomAD v4.1 and 1.33333e-04 in gnomAD v2.1). Human review is retained because RAD51B lacks a retrieved gene-specific framework and disease prevalence/penetrance parameters are not established in this bundle.

Rule

Generic non-VCEP PM2 operating threshold: rare or absent in population databases, operationalized here as frequency below 0.1% (0.001), with interpretation conditioned on disease prevalence, penetrance, and database quality; applied at supporting strength because no RAD51B-specific framework was retrieved.

Evidence considered

• gnomAD v4.1 reports 1 alternate allele among 1,612,890 total alleles (AF 6.20005e-07), with 0 homozygotes; the highest displayed subpopulation AF is 1.09963e-05 in South Asians and 4.31704e-05 in South Asian females.
• gnomAD v2.1 reports 1 alternate allele among 250,880 total alleles (AF 3.98597e-06), with 0 homozygotes; the highest displayed subpopulation AF is 3.28386e-05 in South Asians and 1.33333e-04 in South Asian females.
• gnomAD-Canada v1.0 reports the variant as absent.
• The observed frequencies are below the generic non-VCEP PM2 rarity threshold of 0.1% (0.001), but disease prevalence and penetrance are not sufficiently characterized for a disease-specific maximum credible frequency assessment.

Still missing

• No RAD51B-specific CSPEC/VCEP population rule was retrieved.
• Disease prevalence, penetrance, and a maximum credible population frequency estimate were not documented for the relevant RAD51B disorder.
• The variant is observed once in gnomAD rather than completely absent, so the evidence supports rarity rather than absolute absence.

Sources

Reasoning

BP3 (Richards et al. 2015, PMID 25741868) applies to in-frame insertions/deletions in a repeat region without a known function. NM_133509.4:c.171_173dupCAG is an in-frame duplication of one CAG repeat unit (reference CAG[2] at c.168-173; variant CAG[3]) resulting in p.(Ser57dup) / p.Ser57_Arg58insSer — a single-amino-acid in-frame insertion in a tandem trinucleotide repeat region. The repeat region has no documented function: it lies in the N-terminal portion of RAD51B (residue 57 of 385) in exon 3, upstream of the characterized Walker A ATPase motif (GPPGCGKT, starting ~residue 108); no literature or functional studies for this variant or this repeat tract were identified (literature_pass total_pmids=0; fulltext_map empty; OncoKB has no variant-specific functional evidence); and RAD51B is not associated with any repeat-expansion disorder. SpliceAI predicts no splice impact (max delta 0.09), consistent with the change acting as a purely in-frame protein-level insertion. BP3 is therefore met at supporting (benign) strength. Per the governing generic ACMG/AMP framework (PMID 25741868), BP3 and PM4 are mutually exclusive for this variant; the repeat-region context directs this variant to BP3.

Rule

generic_acmg_BP3

Evidence considered

• ClinVar variation 3942256 variant title 'NM_133510.4(RAD51B):c.168CAG[3] (p.Ser57_Arg58insSer)' confirms the variant is an expansion of a tandem CAG repeat from 2 to 3 copies, i.e., an in-frame insertion in a repeat region.
• Transcript-level verification against the NM_133509.4 reference sequence (NCBI): c.168-173 = CAGCAG (tandem CAG repeat); c.171_173dupCAG yields CAGCAGCAG and an in-frame single Ser insertion (p.Ser57dup). The affected residue (Ser57) is in exon 3, N-terminal region, upstream of the Walker A ATPase motif (GPPGCGKT) which begins at residue ~108.
• pvs1_variant_assessment.json: consequence_class=in_frame_indel_unknown, canonical_splice_consensus=false — the change is an in-frame insertion with no NMD or splice-consensus involvement.
• SpliceAI predicts no significant splice impact (max delta score 0.09, DS_AG=0.09; DS_AL=0.001; DS_DG=0.001; DS_DL=0.003), consistent with a purely in-frame protein-level insertion with no splicing consequence.
• No publications were identified for this variant or repeat tract (literature_pass total_pmids=0; fulltext_map.json empty), so no source documents a function for this CAG repeat region.
• RAD51B gene context (gene_context.json; OncoKB gene-level summary) describes RAD51B as a homologous-recombination DNA repair protein/tumor suppressor with disease mechanism of loss of function, but attributes no function to the N-terminal CAG repeat region containing Ser57.
• No official CSPEC/VCEP framework exists for RAD51B (framework_mode=generic_acmg), so generic ACMG/AMP 2015 rules (PMID 25741868) govern BP3.

Still missing

• 'Without a known function' for the N-terminal CAG repeat region is an absence-of-evidence determination: no functional studies of p.(Ser57dup) or of this repeat tract were identified in the case evidence.
• The reference tandem repeat is only two CAG units, and the variant is rare in gnomAD (1/250,880 alleles in v2.1; 1/1,612,890 in v4.1, 0 homozygotes) — BP3 is applied here on structural/functional context grounds, not on allele-frequency grounds, and the variant is not a common polymorphic repeat-length allele.
• ClinVar reports this variant as VUS (single submitter, 1 star); no inference is drawn from ClinVar's final classification, only from its variant title repeat notation.

Sources

Reasoning

No RAD51B-specific CSPEC/VCEP framework or PP3/BP4 lookup spreadsheet is available for this case, so generic ACMG/AMP computational-evidence conventions govern. SpliceAI predicts no significant splice impact for NM_133509.4:c.171_173dup (max delta score = 0.09), well below the ~0.2 high-precision cutoff established in the original SpliceAI publication (Jaganathan et al., Cell 2019, PMID 30661751), and Pangolin donor/acceptor gain/loss scores are similarly negligible (SG=0.032, SL=-0.005). This multiple-tool concordance of low predicted splicing effect supports a benign computational signal, meeting BP4 at supporting strength. The variant's missense in-silico path (REVEL/BayesDel) does not apply since this is an in-frame codon duplication rather than a substitution.

Rule

generic_acmg_BP4

Evidence considered

• SpliceAI scores for NM_133509.4:c.171_173dup: DS_AG=0.09, DS_AL=0.001, DS_DG=0.001, DS_DL=0.003, max_delta_score=0.09; Pangolin SG=0.032, SL=-0.005 (source: spliceai, evidence.json splicing block).
• The SpliceAI developers (Jaganathan KK et al., Cell 2019, PMID 30661751) reported that delta scores below ~0.2 correspond to predicted absence of splice-altering effect at high precision; a max delta of 0.09 is well within this benign-predicted range.
• REVEL and BayesDel are not applicable to this in-frame duplication variant class and are recorded as not found/null in the case evidence, so they contribute no additional BP4 signal here.

Still missing

• No RAD51B-specific VCEP splicing calibration table exists to adjust strength beyond the generic supporting level.

Sources

Reasoning

PM4 (Richards et al. 2015, PMID 25741868) applies to protein length changes caused by in-frame insertions/deletions in a NON-repeat region, or by stop-loss variants. NM_133509.4:c.171_173dupCAG is an in-frame duplication of a single CAG unit of a tandem CAG repeat (reference cDNA c.168-173 = CAGCAG; variant = CAGCAGCAG) producing NP_598193.2:p.(Ser57dup), i.e., a +1 amino acid in-frame protein length change. However, the affected sequence lies within a tandem trinucleotide repeat region — confirmed by ClinVar's own repeat-copy notation for this variant (NM_133510.4(RAD51B):c.168CAG[3], p.Ser57_Arg58insSer), by the Mutalyzer normalization shift of 3 nucleotides indicating repetitive context, and by direct transcript-level inspection of the reference sequence. Because PM4's structural prerequisite requires a non-repeat region, and in-frame indels in repeat regions are governed by the mutually exclusive BP3 rule instead, PM4 is not met. No NMD is triggered (in-frame insertion; pvs1_variant_assessment consequence_class = in_frame_indel_unknown), and the protein length change itself is not disputed — the repeat-region exclusion is the sole basis for not_met.

Rule

generic_acmg_PM4

Evidence considered

• ClinVar variation 3942256 (Ambry Genetics submission SCV006146094) lists the variant title 'NM_133510.4(RAD51B):c.168CAG[3] (p.Ser57_Arg58insSer)' — repeat-copy notation indicating the reference allele carries two tandem CAG units (CAG[2]) and the variant carries three (CAG[3]); this confirms the duplication falls inside a tandem CAG repeat region.
• Transcript-level verification against the NM_133509.4 reference sequence (NCBI): cDNA positions c.168-173 are CAGCAG (two tandem CAG units); c.171_173dupCAG creates CAGCAGCAG, an in-frame insertion of one Ser residue, consistent with NP_598193.2:p.(Ser57dup).
• Mutalyzer normalization of c.171_173dupCAG reports a 3-nucleotide shift (normalized_model shift: 3), indicating the duplication lies in a repetitive sequence context and could be equivalently described at multiple positions within the CAG repeat.
• pvs1_variant_assessment.json classifies the variant as consequence_class=in_frame_indel_unknown and canonical_splice_consensus=false, i.e., an in-frame single-amino-acid insertion that does not trigger NMD and is not a null variant.
• No official CSPEC/VCEP framework exists for RAD51B (framework_mode=generic_acmg; cspec.found=false; gene_vcep_dir=null), so generic ACMG/AMP 2015 rules (PMID 25741868) govern PM4; under those rules PM4 is restricted to in-frame indels in non-repeat regions.

Still missing

• The reference tandem repeat is only two CAG units long; the repeat-region classification is the deciding factor between PM4 (non-repeat) and BP3 (repeat). If a reviewer rejected the repeat-region interpretation, PM4 at moderate strength would become the applicable criterion for this in-frame +1 amino acid change.

Sources

Reasoning

No official CSPEC/VCEP framework exists for RAD51B (framework_mode=generic_acmg; cspec.found=false; gene_vcep_dir=null), so generic ACMG/AMP computational-evidence conventions apply. The variant NM_133509.4:c.171_173dup (p.(Ser57dup)) is an in-frame duplication of a single codon, not a missense or synonymous substitution, so REVEL/BayesDel/aGVGD missense predictors are not biologically applicable (and are in fact recorded as not found/null in this case's evidence: revel.score=null, bayesdel.score=null). The only relevant deleterious-direction in-silico signal available is SpliceAI, which predicts no significant splice impact (max delta score 0.09, well below the ~0.2 high-precision threshold established by the SpliceAI developers), so there is no computational evidence pointing toward a damaging/pathogenic effect. PP3 is therefore not met.

Rule

generic_acmg_PP3

Evidence considered

• SpliceAI scores for NM_133509.4:c.171_173dup: DS_AG=0.09, DS_AL=0.001, DS_DG=0.001, DS_DL=0.003, max_delta_score=0.09; Pangolin SG=0.032, SL=-0.005 (source: spliceai, evidence.json splicing block).
• SpliceAI's original developers (Jaganathan KK et al., Cell 2019, PMID 30661751) established delta score cutoffs (~0.2 for high-precision, ~0.5 higher precision) used to interpret predicted splice-altering effect; a max delta of 0.09 falls well below even the lower-sensitivity 0.2 threshold, indicating no predicted splicing disruption.
• REVEL and BayesDel are not applicable predictors for this variant class (in-frame codon duplication, not a missense substitution); case evidence also records both as score=null/not found.

Still missing

• No missense-specific predictor (REVEL/BayesDel) is applicable because this is an in-frame duplication rather than a substitution.
• No RAD51B-specific VCEP splicing lookup table is available to override the generic SpliceAI interpretation.

Sources

Reasoning

PP5 is not met. ClinVar reports an uncertain-significance submission from a single clinical laboratory with criteria-provided, single-submitter review status; no exact-variant ClinVar expert-panel Pathogenic or Likely pathogenic classification is present. The available submission is not eligible to trigger PP5.

Rule

Apply PP5 only when an exact-variant ClinVar expert-panel classification is Pathogenic or Likely pathogenic; otherwise do not apply it.

Evidence considered

• ClinVar record 3942256 is reported as Uncertain significance with review status criteria provided, single submitter and one laboratory submission.
• The ClinVar record has no expert-panel classification, and its displayed variant title is NM_133510.4(RAD51B):c.168CAG[3] (p.Ser57_Arg58insSer), whereas the case variant is normalized as NM_133509.4:c.171_173dup, p.(Ser57dup).
• Under the requested rule, ordinary laboratory submissions, aggregate labels, non-expert assertions, and non-Pathogenic/ non-Likely pathogenic classifications cannot trigger PP5.

Sources

Reasoning

BA1 is not met. The variant is far below a stand-alone benign population-frequency threshold: gnomAD v4.1 total AF is 6.20005e-07 and the highest reported subpopulation AF is 4.31704e-05 in South Asian females; gnomAD v2.1 total AF is 3.98597e-06 and the highest reported subpopulation AF is 1.33333e-04. These frequencies do not approach the generic BA1 threshold.

Rule

Generic ACMG/AMP BA1: stand-alone benign when the allele frequency is greater than 5% or another applicable validated threshold; this variant does not meet that frequency requirement.

Evidence considered

• gnomAD v4.1 reports 1 alternate allele among 1,612,890 total alleles (AF 6.20005e-07), with the highest displayed subpopulation frequency 1/23,164 alleles (AF 4.31704e-05) in South Asian females.
• gnomAD v2.1 reports 1 alternate allele among 250,880 total alleles (AF 3.98597e-06), with the highest displayed subpopulation frequency 1/7,500 alleles (AF 1.33333e-04) in South Asian females.
• The observed frequencies are well below the generic stand-alone BA1 population-frequency threshold.

Sources

Reasoning

BS1 is not met. The maximum observed population frequency is 1.33333e-04 in gnomAD v2.1 South Asian females and 4.31704e-05 in gnomAD v4.1 South Asian females, with overall frequencies of 3.98597e-06 and 6.20005e-07, respectively. These values are below the generic non-VCEP BS1 threshold of 0.3% (0.003), and no disease-specific frequency threshold is available because no RAD51B CSPEC/VCEP framework was retrieved.

Rule

Generic non-VCEP BS1 operating threshold: allele frequency greater than 0.3% (0.003), subject to disease prevalence and penetrance; no disease-specific RAD51B threshold was available.

Evidence considered

• gnomAD v2.1 reports total AF 3.98597e-06 and highest displayed subpopulation AF 1.33333e-04 in South Asian females.
• gnomAD v4.1 reports total AF 6.20005e-07 and highest displayed subpopulation AF 4.31704e-05 in South Asian females.
• Both the overall and highest-subpopulation frequencies are below the generic non-VCEP BS1 threshold of 0.3%.

Still missing

• No RAD51B-specific disease prevalence, penetrance, or maximum credible population frequency threshold was available.

Sources

Reasoning

BS2 is not met. The variant has zero reported homozygotes in both gnomAD v2.1 and gnomAD v4.1, and no healthy homozygous or hemizygous observation supporting tolerance was provided. Absence of homozygotes does not itself establish pathogenicity, but it provides no BS2 evidence.

Rule

Generic ACMG/AMP BS2: observation in healthy adults in a homozygous or hemizygous state, when the disease is expected to be fully penetrant early in life; no such observation is present.

Evidence considered

• gnomAD v2.1 reports 0 homozygotes for the variant in the total dataset and 0 homozygotes in the highest-frequency South Asian subpopulation.
• gnomAD v4.1 reports 0 homozygotes for the variant in the total dataset and 0 homozygotes in the highest-frequency South Asian subpopulation.
• No healthy homozygous or hemizygous individuals were reported in the case evidence bundle.

Sources

Reasoning

BP6 is not met. ClinVar reports an uncertain-significance single-submitter laboratory assertion and no exact-variant expert-panel Benign or Likely benign classification. The available record is not eligible to trigger BP6.

Rule

Apply BP6 only when an exact-variant ClinVar expert-panel classification is Benign or Likely benign; otherwise do not apply it.

Evidence considered

• ClinVar record 3942256 is reported as Uncertain significance with review status criteria provided, single submitter and one laboratory submission.
• No exact-variant ClinVar expert-panel Benign or Likely benign assertion is present.
• Under the requested rule, ordinary laboratory submissions, aggregate labels, non-expert assertions, and non-Benign/ non-Likely benign classifications cannot trigger BP6.

Sources

Reasoning

No proband-level de novo observation or documented parental testing is provided for NM_133509.4:c.171_173dup (p.(Ser57dup)). The evidence bundle contains no parental genotypes, maternity/paternity confirmation, or de novo case report sufficient to assess PS2.

Rule

Generic ACMG/AMP PS2: de novo occurrence in a patient with the disease and no family history, with both maternity and paternity confirmed; strength may depend on confirmation and phenotype consistency.

Evidence considered

• The consolidated evidence bundle reports no literature PMIDs and contains no proband, parental, or de novo segregation data.
• No applicable RAD51B VCEP or gene-specific framework was retrieved; generic ACMG/AMP criteria were therefore used only as the fallback framework.

Still missing

• Proband phenotype and case-level clinical report
• Maternal and paternal variant testing results
• Confirmation of biological parentage
• Read-level or orthogonal confirmation of the variant in the proband and parents

Reasoning

No ClinGen VCEP-specific criteria exist for RAD51B (framework_mode: generic_acmg, cspec.found: false); generic ACMG PS3 requires well-established functional assay data demonstrating a damaging effect on protein function. The literature pass returned zero PMIDs (literature_pass.json: total_pmids=0, note='No PMIDs found across evidence sources'), OncoKB found no variant-specific functional evidence for this variant (only gene-level DNA repair context for RAD51B), and no functional/biochemical assay data (e.g., homologous recombination assays, RAD51 focus formation, minigene splicing assays) for NM_133509.4:c.171_173dup / p.(Ser57dup) is present anywhere in the evidence bundle.

Evidence considered

• literature_pass.json reports total_pmids=0 and no criteria_index/criterion_screened entries for PS3
• OncoKB evidence_sentence states no variant-specific reviewed functional evidence was identified for this variant, only gene-level curated context
• case_summary.json cspec.found=false; final_classification_framework.json framework_mode=generic_acmg with framework_complete=false, indicating no RAD51B-specific VCEP PS3 assay guidance is available

Still missing

• No functional assay publications or data identified for this specific variant
• No VCEP-specific PS3 assay validation criteria available for RAD51B
• Literature search returned zero PMIDs

Reasoning

No case-control study, affected-case series, statistically significant enrichment result, or disease-specific carrier count for NM_133509.4:c.171_173dup was provided. The available evidence bundle contains no literature PMIDs or phenotype prevalence data sufficient to assess PS4.

Rule

Generic ACMG/AMP PS4: assess statistically significant enrichment of the variant in affected individuals compared with controls, or a sufficiently characterized affected-case series; no applicable RAD51B VCEP specification was retrieved.

Evidence considered

• The case summary reports no PMIDs across evidence sources and the literature pass has an empty criteria index.
• The bundle contains no disease-specific case-control or affected-case phenotype dataset for this variant.

Still missing

• Disease-specific affected-case and control counts for this exact variant are unavailable.
• No case-control enrichment statistics or adequately characterized affected-case series are available.

Reasoning

No affected-proband observations, biallelic disease reports, pathogenic or likely pathogenic partner variant, phase information, or inheritance data are documented for NM_133509.4:c.171_173dup (p.(Ser57dup) in RAD51B). The available case bundle contains no evidence sufficient to assess PM3.

Evidence considered

• The case-evidence bundle identifies RAD51B and normalizes the variant as NM_133509.4:c.171_173dup, NP_598193.2:p.(Ser57dup), but provides no affected-proband, compound-heterozygous, phase, or inheritance observations.
• The bundle reports no literature PMIDs for this exact variant and no applicable RAD51B VCEP/CSPEC framework; ClinVar contains only a single-submitter uncertain-significance record and does not provide allelic evidence for PM3.

Still missing

• Affected-proband case observations are unavailable.
• No pathogenic or likely pathogenic second RAD51B variant is documented.
• No cis/trans phase information is available.
• No inheritance or segregation data are available.

Reasoning

No suspected de novo occurrence is documented for this variant. There is no parental testing, parentage information, or case-level evidence establishing a de novo event without confirmed maternity and paternity; PM6 cannot be assessed.

Rule

Generic ACMG/AMP PM6: assumed de novo occurrence, but without confirmation of maternity and paternity.

Evidence considered

• The consolidated evidence bundle contains no de novo report, parental testing result, meiosis information, or phenotype description for the proband.
• No specific publication was relevant to PM6 because the literature pass found no PMIDs for this case variant.

Still missing

• Documented suspected de novo case observation
• Maternal and paternal genotypes
• Parentage confirmation
• Phenotype consistency with the relevant RAD51B-associated disorder

Reasoning

No familial segregation data are available. The bundle does not identify affected relatives, unaffected relatives, informative meioses, variant-positive relatives, or variant-negative relatives; therefore supportive co-segregation cannot be assessed.

Rule

Generic ACMG/AMP PP1: co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease; strength requires evaluation of informative meioses and phenotype specificity.

Evidence considered

• The consolidated evidence bundle has no family history, pedigree, relative genotypes, segregation counts, or phenotype-segregation observations.
• No publication was reviewed for PP1 because no case-level publication or PMID was identified in the evidence bundle.

Still missing

• Pedigree and number of informative meioses
• Phenotypes and diagnostic status of relatives
• Genotypes of affected and unaffected relatives
• Specification of whether segregation is independent or duplicated across reports

Reasoning

The case bundle does not provide the patient's phenotype, a confirmed specific disorder, or a phenotype specificity assessment. PP4 therefore cannot be evaluated.

Rule

Generic ACMG/AMP PP4: the patient's phenotype or family history is highly specific for a disease with a single-gene etiology; no applicable RAD51B VCEP specification was retrieved.

Evidence considered

• The consolidated case evidence contains variant normalization and database results but no patient phenotype or disease-specific clinical description.

Still missing

• Patient phenotype and clinical presentation are not available.
• A specific disease diagnosis and assessment of phenotype specificity for RAD51B-related disease are not available.

Reasoning

No ClinGen VCEP-specific criteria exist for RAD51B (framework_mode: generic_acmg, cspec.found: false); generic ACMG BS3 requires well-established functional assay data showing no damaging effect on protein function or splicing. No such functional/biochemical assay evidence for NM_133509.4:c.171_173dup / p.(Ser57dup) is present anywhere in the evidence bundle, and the literature pass returned zero PMIDs.

Evidence considered

• literature_pass.json reports total_pmids=0 and no criteria_index/criterion_screened entries for BS3
• OncoKB evidence_sentence states no variant-specific reviewed functional evidence was identified for this variant, only gene-level curated context
• case_summary.json cspec.found=false; final_classification_framework.json framework_mode=generic_acmg with framework_complete=false, indicating no RAD51B-specific VCEP BS3 assay guidance is available

Still missing

• No functional assay publications or data identified for this specific variant
• No VCEP-specific BS3 assay validation criteria available for RAD51B
• Literature search returned zero PMIDs

Reasoning

No non-segregation evidence is provided. There are no documented unaffected, appropriately aged relatives who carry the variant, and no phenotype/genotype information allowing assessment of whether the variant fails to segregate with disease.

Rule

Generic ACMG/AMP BS4: lack of segregation in affected members of a family; assessment requires an informative pedigree and reliable disease/variant status for relatives.

Evidence considered

• The consolidated evidence bundle contains no relatives, pedigree, parental or familial genotypes, or non-segregation observations.
• Absence of segregation data is insufficient to call BS4 met or not_met.

Still missing

• Genotypes of unaffected relatives
• Ages and clinical evaluation of unaffected carriers
• Pedigree structure and informative meioses
• Disease penetrance and phenotype ascertainment relevant to interpreting non-segregation

Reasoning

No observation is documented of NM_133509.4:c.171_173dup in trans or cis with a pathogenic or likely pathogenic variant in an affected or unaffected individual. The case bundle contains no phase, partner-variant, or inheritance data sufficient to assess BP2.

Evidence considered

• The case-evidence bundle contains no report of this variant occurring with a pathogenic or likely pathogenic variant in cis or in trans.
• The available ClinVar record is a single-submitter uncertain-significance submission and provides no phase or partner-variant evidence relevant to BP2.

Still missing

• No affected or unaffected individual-level allelic observations are available.
• No pathogenic or likely pathogenic partner variant is documented.
• No cis/trans phase information is available.
• No inheritance or family segregation data are available.

Reasoning

No information is available showing that the phenotype is explained by a pathogenic variant in another gene or by another molecular diagnosis. BP5 cannot be assessed from the available bundle.

Rule

Generic ACMG/AMP BP5: a pathogenic variant in another gene explains the patient's phenotype; no applicable RAD51B VCEP specification was retrieved.

Evidence considered

• The case bundle provides no alternate-gene finding, pathogenic comparator, or clinical molecular-diagnosis information relevant to BP5.

Still missing

• No alternate pathogenic molecular diagnosis or explanatory variant is documented.
• No clinical or molecular evidence is available to determine whether another diagnosis explains the phenotype.