Fetal anomalies
Gene: SHANK3

SHANK3 (SH3 and multiple ankyrin repeat domains 3)
EnsemblGeneIds (GRCh38): ENSG00000251322
EnsemblGeneIds (GRCh37): ENSG00000251322
OMIM: 606230, Gene2Phenotype
SHANK3 is in 6 panels

5 reviews

Ida Ertmanska (Genomics England Curator)

This gene and phenotype were reviewed during meetings in July and August 2026. The meetings included representatives of the North Thames and Central and South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler & Louise Carr (North Thames GLH), Sarah Graham & Elizabeth Young (Central & South GLH), and Alice Gardham, Esther Kinning, Vicki Harrison, Anna DeBurca, Natalie Canham, Sunayna Best, Soo-Mi Park & Tessa Homfray (R21 Clinical Oversight Group).
Created: 29 Oct 2026, 4:13 p.m. | Last Modified: 29 Oct 2026, 4:13 p.m.

Panel Version: 8.26

Created: 29 Oct 2026, 4:13 p.m.
Last Modified: 29 Oct 2026, 4:13 p.m.
Panel version: 8.26

Sarah Graham (West Midlands Regional Genetics Laboratory, Birmingham Women's and Children’s NHS Foundation Trust)

I don't know

Pheland-McDermid syndrome - predominantly neurodevelopmental disorder diagnosed postnatally but some affected individuals have features that may be detected prenatally. In cases diagnosed prenatally, anomalies on ultrasound included fetal growth restriction, cardiac and renal anomalies, jejunal atresia, ascites, ventriculomegaly (PMID: 36118903). Prenatally-diagnosed cases typically have large deletions and/or ring 22 rather than sequence variants (eg PMID: 40049821). Deletions account for >85% of cases overall. GeneReviews states cardiac abnormalities in 13% (including aortic regurgitation, patent ductus arteriosus, total anomalous venous return, atrial septal defect, and tricuspid valve regurgitation), renal issues in 13% (including cystic kidneys, renal agenesis or dysplastic kidneys, hydronephrosis or pyelectasis, vesicoureteral reflux and horseshoe kidney), abnormal brain imaging in 49% (including delayed myelination, agenesis of the corpus callosum, ventriculomegaly, white matter atrophy and other white matter abnormalities, generous extracerebral space, large cisterna magna, and arachnoid cyst) (https://www.ncbi.nlm.nih.gov/books/NBK1198/) Red on Australian fetal anomalies panel.
Created: 29 Oct 2026, 3:51 p.m. | Last Modified: 29 Oct 2026, 3:51 p.m.

Panel Version: 8.25

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Phelan-McDermid syndrome, OMIM:606232

Created: 29 Oct 2026, 3:51 p.m.
Last Modified: 29 Oct 2026, 3:51 p.m.
Panel version: 8.25

Arina Puzriakova (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 3 Mar 2022, 11:19 a.m. | Last Modified: 3 Mar 2022, 11:19 a.m.

Panel Version: 1.836

Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Created: 1 Feb 2021, 5:27 p.m. | Last Modified: 1 Feb 2021, 5:27 p.m.

Panel Version: 1.588

Created: 1 Feb 2021, 5:27 p.m.
Last Modified: 1 Feb 2021, 5:27 p.m.
Panel version: 1.836

Rhiannon Mellis (Great Ormond Street Hospital)

Green List (high evidence)

This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Primary lymphoedema
Created: 28 Jan 2021, 3:15 p.m. | Last Modified: 28 Jan 2021, 3:15 p.m.

Panel Version: 1.192

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
PHELAN-MCDERMID SYNDROME

Created: 28 Jan 2021, 3:15 p.m.
Last Modified: 28 Jan 2021, 3:15 p.m.
Panel version: 1.192

Rebecca Foulger (Genomics England curator)

I don't know

DDG2P rating in original PAGE list: Probable for PHELAN-MCDERMID SYNDROME
Created: 11 Dec 2018, 9:05 a.m.

Created: 11 Dec 2018, 9:05 a.m.

Panel version: 0.9

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

NHS GMS
Expert Review Green
PAGE DD-Gene2Phenotype

Phenotypes

Phelan-McDermid syndrome, MONDO:0011652
Phelan-McDermid syndrome, OMIM:606232

Tags

Q3_26_demote_amber

OMIM

606230

Clinvar variants

Variants in SHANK3

Penetrance

None

Panels with this gene

History Filter Activity

2 Nov 2026, Gel status: 3

Added Tag

Ida Ertmanska (Genomics England Curator)

Tag Q3_26_demote_amber tag was added to gene: SHANK3.

29 Oct 2026, Gel status: 3

Added New Source, Set Phenotypes

Ida Ertmanska (Genomics England Curator)

Source NHS GMS was added to SHANK3. Added phenotypes Phelan-McDermid syndrome, OMIM:606232 for gene: SHANK3

3 Mar 2022, Gel status: 3