Hereditary cancer panel

MSH2 c.2083G>A

p.Val695Met · Lynch syndrome

No material changeNo review requiredVCV000633496 rs772491283

Then and now

Current evidence agrees with the interpretation on record.

Then2022

Pathogenic

As reported

Science
changed

Now2018

Pathogenic

Reviewed by expert panel

Evidence summary

Decision support

Current evidence for MSH2 c.2083G>A agrees with the pathogenic interpretation issued in 2022. The classification was last evaluated on 18 Oct 2018 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	18 Oct 2018	Strong3 of 4 review criteria met	VCV000633496
Population frequencyHighest reported allele frequency carried on the source record.	Not reported	No frequency data	18 Oct 2018	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.	Pathogenic	Internal report	19 May 2022	On record

Cited publications

Saturation-scale functional evidence supports clinical variant interpretation in Lynch syndrome. — Genome Biol 2022 · PMID 36550560
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
European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender. — Br J Surg 2021 · PMID 34043773
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
Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk. — Am J Hum Genet 2021 · PMID 33357406
Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. — Gut 2020 · PMID 31672839
Lynch Syndrome in Urologic Malignancies - What Does the Urologist Need to Know? — Urology 2019 · PMID 31302137
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. — Genet Med 2017 · PMID 28492532

How the interpretation changed

MSH2 c.2083G>A — the DNA is unchanged. The evidence around it is not.

2022Genetic test performedFirst record on file carrying MSH2 c.2083G>A.
2022Reported as pathogenicClassified as pathogenic by expert-panel criteria. Surveillance pathway initiated at the time of reporting.
2018Submissions accumulated6 independent submissions now contribute to the classification.
TodayVariantPulse identified the affected records4 historical records carry this variant and were flagged for clinical review.

How VariantPulse reached this resultEight steps, each one inspectable

1Historical record retrievedMSH2 c.2083G>A reported as Pathogenic on 2022-05-19.
2Variant normalisedResolved to ClinVar VCV000633496 (rs772491283) and keyed as MSH2:c.2083G>A.
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 comparedNo regional evidence is held for this variant.
6Impacted records identified12,482 findings checked; 4 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-11201	45-54	19 May 2022	Pathogenic	Pathogenic	Gastroenterology	Dr. M. Suleiman	2y ago	Closed
VP-11244	35-44	30 Jul 2022	Pathogenic	Pathogenic	Clinical Genetics	Dr. L. Haddad	3y ago	Closed
VP-11352	55-64	22 Nov 2022	Pathogenic	Pathogenic	Oncology	Dr. R. Okonjo	3y ago	Closed
VP-11408	65+	15 Mar 2023	Pathogenic	Pathogenic	Gastroenterology	Dr. H. Nassar	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

18 Oct 2018

Strong

VCV000633496

Population frequencyHighest reported allele frequency carried on the source record.

Not reported

No frequency data

18 Oct 2018

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.

Pathogenic

Internal report

19 May 2022

On record

Record

Age band

Test date

As reported

Current

Department

Clinical owner

Last contact

Review state

VP-11201

45-54

19 May 2022

Pathogenic

Gastroenterology

Dr. M. Suleiman

2y ago

Closed

VP-11244

35-44

30 Jul 2022

Pathogenic

Clinical Genetics

Dr. L. Haddad

3y ago

Closed

VP-11352

55-64

22 Nov 2022

Pathogenic

Oncology

Dr. R. Okonjo

3y ago

Closed

VP-11408

65+

15 Mar 2023

Pathogenic

Gastroenterology

Dr. H. Nassar

3y ago

Closed