The BRCA2 c.2471T>C (p.Leu824Ser) variant has not been observed in COSMIC and has been reported in ClinVar, where the current expert-panel classification is likely benign.1 This variant is present at low frequency in population databases, including 2/237562 alleles in gnomAD v2.1 and 4/1602664 alleles in gnomAD v4.1, with v2.1 grpmax FAF 1.975e-05 and v4.1 grpmax FAF 2.98e-05; these values are below the ENIGMA BA1 and BS1 thresholds and do not support PM2 because the variant is not absent from controls.2 Computational evidence supports a benign interpretation under the BRCA2 ENIGMA framework because p.Leu824Ser lies outside the BRCA2 clinically important domains used for missense evaluation, SpliceAI predicts no significant splice effect with a maximum delta score of 0.01, BayesDel is -0.270943, and REVEL is 0.261, supporting BP1_Strong and not supporting PP3.3 The BRCA2 clinical-history likelihood ratio is 0.60 in 2 probands, which falls in the neutral zone and does not support either PP4 or BP5.4
BRCA2
Final classification
Likely Benign
BRCA2 c.2471T>C · p.Leu824Ser
BRCA2
The BRCA2 c.2471T>C (p.Leu824Ser) variant has not been observed in COSMIC and has been reported in ClinVar, where the current expert-panel classification is likely benign.
ENIGMA BRCA1/BRCA2 Specification v1.2 Table 3 final-classification framework from the official CSPEC/VCEP source.
Classification rationale
BP1BP6
Likely Benign
BRCA2 c.2471T>C
BP1 + BP6
→
Likely Benign
3
cspec ↗spliceai ↗bayesdelrevel
4
cspec ↗vcep_pmid_31853058_brca2_clinical_history_lrPMID:31853058 ↗
Gene diagram
· NM_000059.3 · variants mapped to exon structure
BRCA2
NM_000059.3
Fetching transcript structure from UCSC…
Applied criteria · 2 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= 2.49584e-06; MAF= 0.00025%, 4/1602664 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 8.92379e-05; MAF= 0.00892%, 4/44824 alleles, homozygotes = 0); grpmax FAF= 2.98e-05.
v2.1
This variant is present in gnomAD v2.1 (AF= 8.41885e-06; MAF= 0.00084%, 2/237562 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000113507; MAF= 0.01135%, 2/17620 alleles, homozygotes = 0); grpmax FAF= 1.975e-05.
Allele frequency by ancestry
three datasets · side by side
gnomAD v4.1
0.00025%
· 4 / 1,602,664
0 hom · FAF 0.003%
0 hom · FAF 0.003%
East Asian 4 / 44,824 |
0.0089% |
+ 9 not observed (Remaining individuals, Admixed American, European (Finnish), Amish, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American, European (non-Finnish))
gnomAD v2.1
0.00084%
· 2 / 237,562
0 hom · FAF 0.002%
0 hom · FAF 0.002%
East Asian 2 / 17,620 |
0.011% |
+ 7 not observed (African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), European (non-Finnish), Remaining individuals, South Asian)
ClinVar
This variant has been reported in ClinVar as Uncertain significance (4 clinical laboratories) and as Likely pathogenic (1 clinical laboratory) and as Uncertain Significance (1 clinical laboratory) and as Likely Benign by ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen (expert panel).
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.261. BayesDel score = -0.270943.
Functional
Unknown Oncogenic Effect
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BRCA2, a tumor suppressor involved in the DNA damage response, is mutated in various cancer types.
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.
Literature · how each cited paper was used
1papers cited
Each card is an audit: what was searched, what was found, whether it names the variant, which criteria it fed, and why.
PMID cspec
Found
Structured finding pending for this record — see source link.
Applied to
→BP1 supports · met
→BP6 supports · met
Sources & reference links