VP-R-2026-012

BRCA2 c.9538C>T

Hereditary breast and ovarian cancer

Needs reviewLow

Your DNA didn’t change. Science did. AI assists. Clinicians decide.

Classification change

2023 · On file

Uncertain significance

Reported 24 Apr 2023

Science evolves

Today · ClinVar

Benign

ClinVar last evaluated 18 Aug 2025 · Reviewed by expert panel

The DNA has not changed. Only the interpretation has.BRCA2 c.9538C>T (p.Leu3180Phe) · identical in both

Evidence weakened

Variant

Gene: BRCA2
HGVS (coding): c.9538C>T
Protein: p.Leu3180Phe
ClinVar: VCV000052865
dbSNP: rs200598289
Panel: Hereditary cancer panel
Molecular consequence: missense variant

How the interpretation changed

BRCA2 c.9538C>T. The DNA is unchanged. The evidence around it is not.

2023Genetic test performedFirst record on file carrying BRCA2 c.9538C>T.
2023Reported as uncertain significanceMissense change in the C-terminal region. Reported as uncertain significance.
2025Submissions accumulated13 independent submissions now contribute to the classification.
2025Classification now benignLast evaluated 18 Aug 2025 · Reviewed by expert panel.
TodayVariantPulse identified the affected records2 historical records carry this variant and were flagged for clinical review.

Evidence summary draft

AI draft · clinician must review

Evidence summary

Decision support

Accumulated evidence now favours a more benign reading of BRCA2 c.9538C>T than the uncertain significance interpretation issued in 2023; the current consensus is benign. Where the original result drove additional testing or surveillance, that basis may have weakened. 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.

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.9538C>T

VUSBenign

VP-10765

Not reviewed

45-54 · Breast Surgery

Synthetic ID: VP-10765
Test date: 24 Apr 2023
Original classification: Uncertain significancereported 24 Apr 2023
Current evidence: BenignClinVar, evaluated 18 Aug 2025
Clinical owner: Dr. N. Farouk
Review status: Not reviewed

Open record

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
ClinVar13 submissions on record.	Benign	Reviewed by expert panel	18 Aug 2025	Strong3 of 4 review criteria met	VCV000052865
Population frequencyHighest reported allele frequency carried on the source record.	0.00020	1000 Genomes Project	18 Aug 2025	Reference observation
LiteraturePublications linked to this variant record.	8 indexed publications	PubMed index	Latest 2022	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	24 Apr 2023	On record

Cited publications

Genetic Testing and Its Clinical Application in Prostate Cancer Management: Consensus Statements from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology. · Front Oncol 2022 · PMID 35924163
ACMG SF v3.1 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG). · Genet Med 2022 · PMID 35802134
Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021. · Ann Oncol 2021 · PMID 34242744
ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). · Genet Med 2021 · PMID 34012068
Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer: ASCO Guideline Update. · J Clin Oncol 2021 · PMID 33497248
Risk assessment and genetic counseling for hereditary breast and ovarian cancer syndromes-Practice resource of the National Society of Genetic Counselors. · J Genet Couns 2021 · PMID 33410258
Epidemiological and ES cell-based functional evaluation of BRCA2 variants identified in families with breast cancer. · Hum Mutat 2021 · PMID 33314489
WT1 Disorder. · University of Washington, Seattle 1993 · PMID 32352694

How VariantPulse reached this resultEight steps, each one inspectable

1Historical record retrievedBRCA2 c.9538C>T reported as Uncertain significance on 2023-04-24.
2Variant normalisedResolved to ClinVar VCV000052865 (rs200598289) and keyed as BRCA2:c.9538C>T.
3Current evidence retrievedRead live from ClinVar: Benign, 13 submissions, reviewed by expert panel.
4Classification difference detectedRecorded interpretation normalised to Uncertain significance. Current interpretation normalised to Benign. Evidence moved toward a benign interpretation.
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.

+10Evidence weakenedCurrent evidence favours a more benign reading than the one on record.
+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 score30

Case trail

Every review action on this case, with who took it and when.

No review actions on this case yet.

Recommendation

Review whether surveillance driven by the original interpretation is still indicated for 2 records.

Review actions

Each action is recorded in the audit trail. None changes a classification or a diagnosis.

Assign reviewer

Clinician note

Decision

A decision needs a clinician note of at least 10 characters. It records the outcome of the review; it does not write to any patient record or issue a diagnosis.

Case detail

Case: VP-R-2026-012
Raised: 1m ago
Assigned: Unassigned
Evidence source: ClinVar · Evidence monitor live
Records impacted: 2

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

Affected records in full

Synthetic demonstration data

Record	Age band	Test date	As reported	Current	Department	Clinical owner	Last contact	Review state
VP-10765	45-54	24 Apr 2023	VUS	Benign	Breast Surgery	Dr. N. Farouk	3y ago	Not reviewed
VP-10802	35-44	16 Oct 2023	VUS	Benign	Clinical Genetics	Dr. L. Haddad	3y ago	Not reviewed

Source

Classification

Review level

Last updated

Strength

ClinVar13 submissions on record.

Benign

Reviewed by expert panel

18 Aug 2025

Strong

VCV000052865

Population frequencyHighest reported allele frequency carried on the source record.

0.00020

1000 Genomes Project

18 Aug 2025

Reference observation

LiteraturePublications linked to this variant record.

8 indexed publications

PubMed index

Latest 2022

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

24 Apr 2023

On record

Record

Age band

Test date

As reported

Current

Department

Clinical owner

Last contact

Review state

VP-10765

45-54

24 Apr 2023

VUS

Benign

Breast Surgery

Dr. N. Farouk

3y ago

Not reviewed

VP-10802

35-44

16 Oct 2023

VUS

Benign

Clinical Genetics

Dr. L. Haddad

3y ago

Not reviewed