Laterality disorders and isomerism

Gene: NODAL

Red List (low evidence)

The rating of this gene has been updated to Red following NHS Genomic Medicine Service approval.

Created: 31 Jan 2023, 1:07 p.m. | Last Modified: 31 Jan 2023, 1:07 p.m.

Panel Version: 2.3

Association of NODAL with heterotaxy disorders was discussed at GenCC meeting (13/09/2022) and it was agreed that the evidence is MODERATE for this gene-disease association. Multiple cases where variants were inherited from unaffected parents indicating that this gene is likely conferring a risk with reduced penetrance for the phenotype.

Created: 14 Oct 2022, 9:33 a.m. | Last Modified: 14 Oct 2022, 9:33 a.m.

Panel Version: 1.51

Updating tags to be Q3_22_expert_review and Q3_22_rating so that gene is included in the next GMS report (Oct 2022)

Created: 5 Oct 2022, 11:31 p.m. | Last Modified: 5 Oct 2022, 11:31 p.m.

Panel Version: 1.51

This gene has been tagged for GMS expert review.

Created: 4 May 2021, 10:10 a.m. | Last Modified: 4 May 2021, 10:10 a.m.

Panel Version: 1.44

Red List (low evidence)

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). All of these variants would be VOUS or worse using ACMG criteria. Consider downgrading on all other panels.

Created: 11 May 2020, 10:37 a.m. | Last Modified: 11 May 2020, 10:37 a.m.

Panel Version: 1.5

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Heterotaxy, visceral, 5 (MIM#270100)

Publications

• 9354794
• 19064609

Green List (high evidence)

On CGGL Royal Brompton panel. Good literature evidence (Mohapatra et al 2009) and good experimental evidence.

Created: 25 Nov 2019, 11:15 p.m. | Last Modified: 25 Nov 2019, 11:15 p.m.

Panel Version: 0.51

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

Phenotypes
OMIM Heterotaxy, visceral, 5270100

Publications

• 19064609

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

From Panel Familial non syndromic congenital heart disease. 4 Jul 2017, 7:24 a.m. Panel version: 1.8. Review by Helen Brittain (Genomics England Curator). Green List (high evidence). In 14/269 cases with heterotaxy and or cardiovascular malformations, mutations identified in listed PMID. Mutations included missense, splice site and an in-frame indel.
Mode of inheritance MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown. Phenotypes: Heterotaxy syndrome; Heterotaxy, visceral, 5, 270100; Visceral Heterotaxy; Heterotaxy, Visceral, 5, Autosomal. Publications: 19064609

Created: 16 Jan 2019, 1:31 p.m.

Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: NODAL; Suggested initial gene rating: Green; Evidence for inclusion: OMIM PCD or Visceral heterotaxy gene; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given

Created: 5 Dec 2018, 12:52 p.m.

Publications

• 19064609