Evidence map›Paper›PMID 42316767›Full record

ArticlePrenatal diagnosis2026

Is There Potential Clinical Utility in Reporting Variants of Uncertain Significance From Prenatal Sequencing?

A Gibbs, R Braham, V Ramachandran, R Roberts, C Willison, T Ashraf, J Cobben, A Gardham, M Holder-Espinasse, T Homfray and 4 more

Abstract read
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Article in Prenatal diagnosis, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

A GibbsNHS North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.ORCID https://orcid.org/0009-0003-5387-7420
R BrahamNHS North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.ORCID https://orcid.org/0009-0005-9629-2136
V RamachandranNHS North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.ORCID https://orcid.org/0009-0004-9286-5462
R RobertsNHS North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
C WillisonNHS North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
T AshrafDepartment of Clinical Genetics, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.ORCID https://orcid.org/0000-0002-1081-6965
J CobbenCentre for Fetal Care, Queen Charlotte Hospital, ICHT NHS & Imperial College, London, UK.ORCID https://orcid.org/0000-0002-3551-543X
A GardhamDepartment of Clinical Genetics, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.ORCID https://orcid.org/0000-0002-6556-366X
M Holder-EspinasseDepartment of Clinical Genetics, Guy's Hospital, London, UK.
T HomfrayDepartment of Medical Genetics, St George's University of London, London, UK.
S G MehtaDepartment of Clinical Genetics, Addenbrooke's Hospital, Cambridge, UK.ORCID https://orcid.org/0000-0003-0446-3435
D TaponQueen Charlotte's & Chelsea Hospital, Imperial College Healthcare NHS Trust, London, UK.ORCID https://orcid.org/0000-0003-3837-4764
P VasudevanDepartment of Clinical Genetics, University Hospitals of Leicester, Leicester Royal Infirmary, Leicester, UK.
N J ChandlerNHS North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.ORCID https://orcid.org/0000-0003-1396-0740

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivePrenatal sequencing of fetuses with abnormalities detected on imaging is expanding globally. Debate continues over whether variants of uncertain significance (VUS) should be reported prenatally, with some recent national position statements opposing this. In England, VUS that fit the fetal phenotype and require little further evidence for upgrade are discussed at multidisciplinary team (MDT) meetings to determine whether to report. We review the VUS reported by one English laboratory that provides prenatal sequencing to half of England.

methodThe laboratory's database was searched from 01/10/2020 to 30/04/2025 to ascertain all cases where a VUS was reported. Pregnancy outcomes were obtained from local clinical teams to determine whether the VUS status had been resolved.

resultsVUS were reported in 41/881 fetuses sequenced. Follow-up data were available for 38/41 cases, of which 23 were subsequently upgraded to likely pathogenic and 1 downgraded to likely benign. The most common reason for upgrade was new information from post-mortem or postnatal review (17/23).

conclusionThere is clinical utility in reporting VUS from prenatal sequencing following MDT discussion. Although reporting VUS leaves parents with uncertainty, follow up (including post-mortem when applicable) resolves this in over 50% of cases (79% of cases re-examined pre- or postnatally).

Indexed as

Genetic TestingPrenatal DiagnosisEnglandFemaleHumansPregnancyReturn of Individual Research Resultsmultidisciplinary teamprenatalsequencingvariants of uncertain clinical significance

Identifiers

PMID42316767
PMCPMC13571796

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