Hereditary cancer panel

PALB2 c.682C>T

p.Gln228Ter · Hereditary breast cancer

No material changeNo review requiredVCV000484222 rs1327399690

Then and now

Current evidence agrees with the interpretation on record.

Then2022

Pathogenic

As reported

Science
changed

Now2023

Pathogenic

Reviewed by expert panel

Evidence summary

Decision support

Current evidence for PALB2 c.682C>T agrees with the pathogenic interpretation issued in 2022. The classification was last evaluated on 5 Apr 2023 and carries 6 submissions.

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
ClinVar6 submissions on record.	Pathogenic	Reviewed by expert panel	5 Apr 2023	Strong3 of 4 review criteria met	VCV000484222
Population frequencyHighest reported allele frequency carried on the source record.	1.00e-5	The Genome Aggregation Database (gnomAD)	5 Apr 2023	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	Pathogenic	5 regional observations	2 Feb 2026	Cohort 5,400
This institutionThe interpretation issued to the patient at the time of testing.	Pathogenic	Internal report	12 Mar 2022	On record

Cited publications

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
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
Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families. — J Clin Oncol 2020 · PMID 31841383
Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA1/2-Related Cancer in Women: A Systematic Review for the U.S. Preventive Services Task Force — Agency for Healthcare Research and Quality (US) 2019 · PMID 31479213
Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: US Preventive Services Task Force Recommendation Statement. — JAMA 2019 · PMID 31429903
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. — Genet Med 2017 · PMID 28492532

Global and regional evidence

Sources agree

Global

Pathogenic

Submissions: 6
Review status: Reviewed by expert panel
Last evaluated: 5 Apr 2023
Reference frequency: 1.00e-5

Read from ClinVar, which aggregates submissions dominated by European-ancestry cohorts.

Regional

Pathogenic

Observations: 5
Cohort size: 5,400
Last updated: 2 Feb 2026
Regional frequency: 4.60e-4

Modelled regional aggregation maintained inside this workspace.

VariantPulse analysis

Both sources place this variant in the same band, so there is no divergence to resolve. Loss-of-function mechanism is not population dependent. Regional and global readings agree.

How the interpretation changed

PALB2 c.682C>T — the DNA is unchanged. The evidence around it is not.

2022Genetic test performedFirst record on file carrying PALB2 c.682C>T.
2022Reported as pathogenicNonsense change predicted to result in loss of function. Reported as pathogenic with management guidance.
2023Submissions accumulated6 independent submissions now contribute to the classification.
TodayVariantPulse identified the affected records3 historical records carry this variant and were flagged for clinical review.

How VariantPulse reached this resultEight steps, each one inspectable

1Historical record retrievedPALB2 c.682C>T reported as Pathogenic on 2022-03-12.
2Variant normalisedResolved to ClinVar VCV000484222 (rs1327399690) and keyed as PALB2:c.682C>T.
3Current evidence retrievedRead live from ClinVar: Pathogenic, 6 submissions, reviewed by expert panel.
4Classification difference detectedRecorded interpretation normalised to Pathogenic. Current interpretation normalised to Pathogenic. Codes are identical, so no reclassification has occurred.
5Regional sources comparedRegional index asserts Pathogenic, consistent with the global reading.
6Impacted records identified12,482 findings checked; 3 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.

Records carrying this variant

Historical findings in the connected record system that reference this variant.

Record	Age band	Test date	As reported	Current	Department	Clinical owner	Last contact	Review state
VP-10501	45-54	12 Mar 2022	Pathogenic	Pathogenic	Oncology	Dr. R. Okonjo	3y ago	Closed
VP-10534	35-44	25 Apr 2022	Pathogenic	Pathogenic	Breast Surgery	Dr. N. Farouk	3y ago	Closed
VP-10570	55-64	8 Jul 2022	Pathogenic	Pathogenic	Clinical Genetics	Dr. L. Haddad	3y ago	Closed

Recommendation

No action required. Current evidence agrees with the interpretation on record.

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

Source

Classification

Review level

Last updated

Strength

ClinVar6 submissions on record.

Pathogenic

Reviewed by expert panel

5 Apr 2023

Strong

VCV000484222

Population frequencyHighest reported allele frequency carried on the source record.

1.00e-5

The Genome Aggregation Database (gnomAD)

5 Apr 2023

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

Pathogenic

5 regional observations

2 Feb 2026

Cohort 5,400

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

Pathogenic

Internal report

12 Mar 2022

On record

Record

Age band

Test date

As reported

Current

Department

Clinical owner

Last contact

Review state

VP-10501

45-54

12 Mar 2022

Pathogenic

Oncology

Dr. R. Okonjo

3y ago

Closed

VP-10534

35-44

25 Apr 2022

Pathogenic

Breast Surgery

Dr. N. Farouk

3y ago

Closed

VP-10570

55-64

8 Jul 2022

Pathogenic

Clinical Genetics

Dr. L. Haddad

3y ago

Closed