Hereditary cancer panel

BRCA2 c.7847C>T

p.Ser2616Phe · Hereditary breast and ovarian cancer

Classification driftHighVP-R-2026-003VCV000630829 rs1174303167

Then and now

The interpretation moved across the clinically actionable boundary since this result was reported.

2023 · On file

Uncertain significance

Reported 19 Jun 2023

Science evolves

Today · ClinVar

Pathogenic

ClinVar last evaluated 6 Jul 2026 · Reviewed by expert panel

The DNA has not changed. Only the interpretation has.BRCA2 c.7847C>T (p.Ser2616Phe) · identical in both

Patient impact

The changed variant and every historical record that carries it. Select a record to see its detail.

Synthetic demonstration data

Changed variant

BRCA2

c.7847C>T

VUSPathogenic

VP-10395

Not reviewed

35-44 · Oncology

Synthetic ID: VP-10395
Test date: 19 Jun 2023
Original classification: Uncertain significancereported 19 Jun 2023
Current evidence: PathogenicClinVar, evaluated 6 Jul 2026
Clinical owner: Dr. R. Okonjo
Review status: Not reviewed

Open record

Evidence summary

Decision support

Since the 2023 report, the consensus for BRCA2 c.7847C>T has moved from uncertain significance to pathogenic. That reading rests on 7 submissions at strong review confidence, reviewed by expert panel. That crosses the clinically actionable boundary, so management guidance issued on the original interpretation may no longer be the right guidance. 2 records on file carry this variant and have not yet been reassessed.

Composed from the structured fields of the records cited on this page. Requires clinical verification before it informs any decision.

Evidence by source

Each source is shown as it reports itself. VariantPulse does not merge them into a single verdict.

Source	Classification	Review level	Last updated	Strength
ClinVar7 submissions on record.	Pathogenic	Reviewed by expert panel	6 Jul 2026	Strong3 of 4 review criteria met	VCV000630829
Population frequencyHighest reported allele frequency carried on the source record.	0.00e+0	The Genome Aggregation Database (gnomAD), exomes	6 Jul 2026	Reference observation
LiteraturePublications linked to this variant record.	8 indexed publications	PubMed index	Latest 2026	Supporting context
Regional Evidence IndexModelled regional aggregation maintained inside this workspace	No regional record	Not held	-	-
This institutionThe interpretation issued to the patient at the time of testing.	Uncertain significance	Internal report	19 Jun 2023	On record

Cited publications

Comprehensive evidence for the pathogenicity of the BRCA2 c.7847C>T (p.Ser2616Phe) variant specific to the Japanese population. · J Med Genet 2026 · PMID 41856558
The Time Lag Associated With the Reclassification of Germline BRCA Variants' Pathogenicity Is Critical for Cancer Patients. · Cancer Sci 2025 · PMID 40035318
Functional evaluation and clinical classification of BRCA2 variants. · Nature 2025 · PMID 39779857
Saturation genome editing-based clinical classification of BRCA2 variants. · Nature 2025 · PMID 39779848
Evidence-based recommendations for gene-specific ACMG/AMP variant classification from the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel. · Am J Hum Genet 2024 · PMID 39142283
Functional analysis and clinical classification of 462 germline BRCA2 missense variants affecting the DNA binding domain. · Am J Hum Genet 2024 · PMID 38417439
The frequency and pathogenicity of BRCA1 and BRCA2 variants in the general Japanese population. · J Hum Genet 2024 · PMID 38409497
Functional evaluation of BRCA1/2 variants of unknown significance with homologous recombination assay and integrative in silico prediction model. · J Hum Genet 2023 · PMID 37731132

How the interpretation changed

BRCA2 c.7847C>T. The DNA is unchanged. The evidence around it is not.

2023Genetic test performedFirst record on file carrying BRCA2 c.7847C>T.
2023Reported as uncertain significanceMissense change in the DNA-binding domain. Classified as uncertain significance; functional data not yet available.
2024Further literature published7 indexed publications appeared after the original report.
2026Submissions accumulated7 independent submissions now contribute to the classification.
2026Classification now pathogenicLast evaluated 6 Jul 2026 · Reviewed by expert panel.
TodayVariantPulse identified the affected records2 historical records carry this variant and were flagged for clinical review.

How VariantPulse reached this resultEight steps, each one inspectable

1Historical record retrievedBRCA2 c.7847C>T reported as Uncertain significance on 2023-06-19.
2Variant normalisedResolved to ClinVar VCV000630829 (rs1174303167) and keyed as BRCA2:c.7847C>T.
3Current evidence retrievedRead live from ClinVar: Pathogenic, 7 submissions, reviewed by expert panel.
4Classification difference detectedRecorded interpretation normalised to Uncertain significance. Current interpretation normalised to Pathogenic. The interpretation crossed into the clinically actionable band, so records carrying it may need review.
5Regional sources comparedNo regional evidence is held for this variant.
6Impacted records identified12,482 findings checked; 2 carry this variant.
7Evidence brief generatedComposed from the structured fields of the cited records above.
8Human review requestedVariantPulse does not change any record. A clinician decides what happens next.

Review priority

A triage signal for the queue. Not a clinical risk score, and not a statement about any individual.

+60Moved into the actionable bandUncertain significance to Pathogenic.
+102 records on fileHistorical results carrying this variant that a reviewer would reassess.
+10High review confidenceThe current classification carries expert-panel or guideline review.

Ordering score80

Records carrying this variant

The same records as a list, for scanning and screen readers.

Synthetic demonstration data

Record	Age band	Test date	As reported	Current	Department	Clinical owner	Last contact	Review state
VP-10395	35-44	19 Jun 2023	VUS	Pathogenic	Oncology	Dr. R. Okonjo	3y ago	Not reviewed
VP-10432	45-54	4 Sept 2023	VUS	Pathogenic	Clinical Genetics	Dr. M. Suleiman	3y ago	Not reviewed

Recommendation

Reassess 2 records against the current interpretation and decide whether the reporting clinician should be notified. Final interpretation remains with the clinical team.

Decision support only. Final interpretation remains with the qualified clinical team.

Source

Classification

Review level

Last updated

Strength

ClinVar7 submissions on record.

Pathogenic

Reviewed by expert panel

6 Jul 2026

Strong

VCV000630829

Population frequencyHighest reported allele frequency carried on the source record.

0.00e+0

The Genome Aggregation Database (gnomAD), exomes

6 Jul 2026

Reference observation

LiteraturePublications linked to this variant record.

8 indexed publications

PubMed index

Latest 2026

Supporting context

Regional Evidence IndexModelled regional aggregation maintained inside this workspace

No regional record

Not held

This institutionThe interpretation issued to the patient at the time of testing.

Uncertain significance

Internal report

19 Jun 2023

On record

Record

Age band

Test date

As reported

Current

Department

Clinical owner

Last contact

Review state

VP-10395

35-44

19 Jun 2023

VUS

Pathogenic

Oncology

Dr. R. Okonjo

3y ago

Not reviewed

VP-10432

45-54

4 Sept 2023

VUS

Pathogenic

Clinical Genetics

Dr. M. Suleiman

3y ago

Not reviewed