NM_002878.4:c.198G>T (p.Val66=) is a synonymous variant in RAD51D with no predicted amino acid change.1 SpliceAI predicts no splice impact for this variant (max delta score = 0.00), meeting BP7 (supporting).2 This variant is present in gnomAD v4.1 with a grpmax filtering allele frequency of 0.303% and an East Asian subpopulation frequency of 0.348% (156/44,880 alleles, one homozygote), marginally exceeding the 0.3% threshold for BS1 at supporting strength.3 Multiple clinical diagnostic laboratories have classified this variant as Likely benign (5 labs) or Benign (1 lab) in ClinVar (Variation ID: 184496), consistent with BP6 at supporting strength.4 No variant-specific functional, segregation, de novo, or case-control data were identified in the literature. Three PMIDs from ClinVar (25741868, 25394175, 28492532) are guideline or methods papers that do not mention NM_002878.4:c.198G>T.
RAD51D
Final classification
Likely Benign
RAD51D c.198G>T · p.Val66=
RAD51D
NM_002878.4:c.198G>T (p.Val66=) is a synonymous variant in RAD51D with no predicted amino acid change.
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BS1 supporting, BP6 supporting, BP7 supporting; combination = 3 supporting benign, which maps to Likely Benign.
Classification rationale
BS1BP6BP7
Likely Benign
RAD51D c.198G>T
BS1 + BP6 + BP7
→
Likely Benign
Gene diagram
· NM_002878.4 · variants mapped to exon structure
RAD51D
NM_002878.4
Fetching transcript structure from UCSC…
Applied criteria · 3 met · select any tile
Met
Not met
Not assessed
N/A
Strength
very strong
supporting
Pathogenic evidence
PVS
PS
PM
PP
Benign evidence
BA
BS
BP
—
—
—
Rationale
Select a criterion.
Sources
Evidence used
Gaps remaining
Rule
—
Research & evidence
Population frequency · supports benign
gnomAD v4.1
gnomAD v2.1
v4.1
This variant is present in gnomAD v4.1 (AF= 9.72617e-05; MAF= 0.00973%, 157/1614202 alleles, homozygotes = 1) and has highest observed frequency in the East Asian population (AF= 0.00347594; MAF= 0.34759%, 156/44880 alleles, homozygotes = 1); grpmax FAF= 0.00303071.
v2.1
This variant is present in gnomAD v2.1 (AF= 3.57927e-05; MAF= 0.00358%, 9/251448 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000434972; MAF= 0.04350%, 8/18392 alleles, homozygotes = 0); grpmax FAF= 0.00021573.
🇨🇦 CA
Absent from gnomAD-Canada v1.0.
Allele frequency by ancestry
three datasets · side by side
gnomAD v4.1
0.0097%
· 157 / 1,614,202
1 hom · FAF 0.3%
1 hom · FAF 0.3%
East Asian 156 / 44,880 |
0.35% 1 hom |
Remaining individuals 1 / 62,508 |
0.0016% |
+ 8 not observed (Admixed American, European (Finnish), Amish, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American, European (non-Finnish))
gnomAD v2.1
0.0036%
· 9 / 251,448
0 hom · FAF 0.022%
0 hom · FAF 0.022%
East Asian 8 / 18,392 |
0.043% |
Remaining individuals 1 / 6,136 |
0.016% |
+ 6 not observed (African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), European (non-Finnish), South Asian)
gnomAD Canada 🇨🇦
Absent
· 0 / ?
0 hom
0 hom
Not observed in any ancestry group.
ClinVar
This variant has been reported in ClinVar as Likely benign (7 clinical laboratories) and as Benign (1 clinical laboratory). (ClinVarID = 184496)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Functional
Unknown Oncogenic Effect
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
COSMIC
Cancer hotspots
Somatic evidence
Not in COSMIC / hotspots
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Hotspots
This variant does not lie in a statistically significant hotspot.
Sources & reference links
Triaged references · 3 PMIDs not cited in assessment
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.
CLINVAR
25394175 ↗
A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.
CLINVAR
28492532 ↗
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.
CLINVAR