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  3. NODAL
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Fetal anomalies

Gene: NODAL

Amber List (moderate evidence)
NODAL (nodal growth differentiation factor)
EnsemblGeneIds (GRCh38): ENSG00000156574
EnsemblGeneIds (GRCh37): ENSG00000156574
OMIM: 601265, Gene2Phenotype
NODAL is in 8 panels

2 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

I don't know

NODAL is a good biological candidate for heterotaxy disorders, and this is supported by animal models. The gene is depleted for LoF variants in gnomad.

The missense variants reported in PMIDs 9354794 and 19064609 are present at a high population frequency in gnomad, including some in homozygous case: their association with disease is DISPUTED.

A total of at least 7 families reported with severe CHD and high impact variants (stop gain, frameshift and canonical splice site). However, almost invariably these were inherited from unaffected or questionably affected parents (e.g. self reports of heart murmur in childhood), raising questions about whether these variants contribute to disease under a monogenic or polygenic model and/or about penetrance.

Discussed at GenCC on 13/9/2022 and agreed on MODERATE assessment.
Created: 12 Sep 2022, 10:25 p.m. | Last Modified: 12 Sep 2022, 10:25 p.m.
Panel Version: 1.67
Minimal reports and variants in original publications present in gnomAD at a higher than expected frequency. PMID: 9354794 (1997): R183Q reported in affected daughter and unaffected mother. (26 hets; 1 hom in gnomAD) PMID: 19064609 (2009): Reported 4 missense, 1 indel and 2 splice site variants. G260R also found in unaffected individual, concluded to have incomplete penetrance (80 hets in gnomAD); R275C (13 hets in gnomAD); E203K (113 hets and 1 hom)
Created: 11 May 2020, 10:42 a.m. | Last Modified: 11 May 2020, 10:42 a.m.
Panel Version: 0.33

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Heterotaxy, visceral, 5 (MIM#270100)

Publications

Created: 11 May 2020, 10:42 a.m.
Last Modified: 11 May 2020, 10:42 a.m.
Panel version: 1.67

Crystle Lee (Victorian Clinical Genetics Services)

Red List (low evidence)

Minimal reports and variants in original publications present in gnomAD at a higher than expected frequency, originally concluded to be due to incomplete penetrance.

PMID: 9354794 (1997): R183Q reported in affected daughter and unaffected mother. (26 hets; 1 hom in gnomAD)

PMID: 19064609 (2009): Reported 4 missense, 1 indel and 2 splice site variants. G260R also found in unaffected individual, concluded to have incomplete penetrance (80 hets in gnomAD); R275C (13 hets in gnomAD); E203K (113 hets and 1 hom)
Sources: Expert Review
Created: 11 May 2020, 3:21 a.m.

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

Phenotypes
Heterotaxy, visceral, 5 (MIM#270100)

Publications

Created: 11 May 2020, 3:21 a.m.

Panel version: Imported from Heterotaxy panel version 0.36

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Genomics England PanelApp
  • Victorian Clinical Genetics Services
Phenotypes
  • Heterotaxy, visceral, 5 (MIM#270100)
OMIM
601265
Clinvar variants
Variants in NODAL
Penetrance
None
Publications
Panels with this gene

History Filter Activity

12 Sep 2022, Gel status: 2

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: NODAL were set to 9354794; 19064609

12 Sep 2022, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: nodal has been classified as Amber List (Moderate Evidence).

24 Feb 2022, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: nodal has been classified as Red List (Low Evidence).

24 Feb 2022, Gel status: 1

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: NODAL were changed from HETEROTAXY SYNDROME to Heterotaxy, visceral, 5 (MIM#270100)

24 Feb 2022, Gel status: 1

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: NODAL were set to

24 Feb 2022, Gel status: 1

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: NODAL was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

24 Feb 2022, Gel status: 1

Entity classified by Genomics England curator

Chirag Patel (Genetic Health Queensland)

Gene: nodal has been classified as Red List (Low Evidence).

24 Oct 2021, Gel status: 3

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: NODAL was added gene: NODAL was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: NODAL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: NODAL were set to HETEROTAXY SYNDROME