Fetal anomalies
Gene: DCC

DCC (DCC netrin 1 receptor)
EnsemblGeneIds (GRCh38): ENSG00000187323
EnsemblGeneIds (GRCh37): ENSG00000187323
OMIM: 120470, Gene2Phenotype
DCC is in 12 panels

3 reviews

Anna de Burca (Oxford University Hospitals NHS Foundation Trust)

Green List (high evidence)

Definitely worth including as associated with relatively good outcome in ACC. Green
Created: 29 Aug 2024, 8:07 p.m. | Last Modified: 29 Aug 2024, 8:07 p.m.

Panel Version: 4.35

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Mirror movements 1 and/or agenesis of the corpus callosum, OMIM #157600; Gaze palsy, familial horizontal, with progressive scoliosis, 2,OMIM # 617542

Publications

Created: 29 Aug 2024, 8:07 p.m.
Last Modified: 29 Aug 2024, 8:07 p.m.
Panel version: 4.35

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Created: 26 Sep 2024, 11:09 a.m. | Last Modified: 26 Sep 2024, 11:09 a.m.

Panel Version: 4.192

This gene and phenotype were reviewed during meetings between November 2023 & July 2024. The meetings included representatives of the North Thames and Central & South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler, Alison Male and Lyn Chitty (North Thames GLH), Stephanie Allen, Natalie Bibb, Esther Kinning and Denise Williams (Central & South GLH) and Natalie Canham, Anna De Burca and Samantha Doyle R21 Clinical Oversight Group. Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Created: 29 Aug 2024, 8:33 p.m. | Last Modified: 29 Aug 2024, 8:33 p.m.

Panel Version: 4.36

Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Created: 18 Jul 2024, 1:55 p.m. | Last Modified: 18 Jul 2024, 1:55 p.m.

Panel Version: 4.31

Reports with monoalellic variants:

PMID:20431009 reported the identification of a splice site variant in DCC gene in a 4-generation French Canadian family and 1 bp insertion in a five-generation large Iranian family with congenital mirror movements. Incomplete penetrance was observed in these two families (PMIDs: 19127048 & 19720981).

PMID:21242494 reported the identification of a truncating variant in DCC gene in a 3-generation Italian family with in which 4 individuals had mirror movements of the arms and hands with onset in infancy or early childhood.

PMID:28250454 reported the identification of heterozygous DCC variants in individuals from four unrelated multigenerational families with congenital mirror movements and/or agenesis of the corpus callosum.

PMID:31697046 reported the identification of heterozygous frameshift variant in five members of an Ethiopian Jewish family, of which four members were symptomatic, showing reduced penetrance of the variant. Two pregnancies in this family were terminated due to prenatal detection of agenesis of the corpus callosum and dilated lateral ventricles. Only one of these foetuses were tested and carried the variant.

Reports with bialellic variants:

PMID:28250456 reported three individuals from two different families presenting with a similar disorder characterized by global developmental delay, delayed walking, intellectual disability, horizontal gaze palsy, and childhood-onset progressive scoliosis, with age of presentation is at birth in family 1 and at infancy in family 2. One family had a 7.7kb homozygous deletion (p.Pro11Thrfs*15), while the other family had 7bp homozygous deletion (p.Val263Alafs*36). The third family reported with a homozygous missense variant (p.Gln691Lys) did not present with scoliosis.

PMID:33141514 reported the identification of a novel homozygous frameshift variant (p.Asn800Lysfs*11) in three members of a Pakistani family and they presented with mild scoliosis at birth, which continued to increase progressively.

Monoallelic variants in this gene have been associated with relevant phenotypes in OMIM (MIM #157600), but not yet in Gene2Phenotype. Biallelic DCC variants have been associated with relevant phenotypes in OMIM (MIM #617542) and Gene2Phenotype ('definitive' rating on the DD panel).
Created: 18 Jul 2024, 1:52 p.m. | Last Modified: 18 Jul 2024, 1:52 p.m.

Panel Version: 4.27

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Mirror movements 1 and/or agenesis of the corpus callosum, OMIM:157600; Gaze palsy, familial horizontal, with progressive scoliosis, 2, OMIM:617542

Publications

Created: 18 Jul 2024, 1:52 p.m.
Last Modified: 18 Jul 2024, 1:52 p.m.
Panel version: 4.192

Rebecca Foulger (Genomics England curator)

I don't know

DDG2P rating in original PAGE list: Probable for Midline-bridging neuronal commissure disruption, horizontal gaze palsy, scoliosis, and intellectual disability
Created: 11 Dec 2018, 9:04 a.m.

Created: 11 Dec 2018, 9:04 a.m.

Panel version: 0.9

Details

Mode of Inheritance

BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Sources

Expert Review Green
NHS GMS
PAGE DD-Gene2Phenotype

Phenotypes

Mirror movements 1 and/or agenesis of the corpus callosum, OMIM:157600
Gaze palsy, familial horizontal, with progressive scoliosis, 2, OMIM:617542

OMIM

120470

Clinvar variants

Variants in DCC

Penetrance

None

Publications

Panels with this gene