Craniosynostosis

Region: ISCA-37420-Loss

17q21.3 recurrent region (includes KANSL1) Loss

Amber List (moderate evidence)

Chromosome: 17
GRCh38 Position: 45608879-46087510
Haploinsufficiency Score: Sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype
Triplosensitivity Score:
Required percent of overlap: 80%
Variant types: CNV Loss

1 review

Eleanor Williams (Genomics England Curator)

I don't know

GMS Musculoskeletal test group informed of amber rating at Webex. No objections.
Created: 17 Sep 2019, 12:33 p.m. | Last Modified: 17 Sep 2019, 12:33 p.m.
Panel Version: 1.133
Comment on list classification: Upgrading from red to amber as some evidence of association of the CNV loss with craniosynostosis. Will discuss on Webex with GMS Musculoskeletal test group
Created: 6 May 2019, 11:04 a.m.
PMID: 26424144 - Zollino et al 2015 – 1 patient with craniosynostosis and 17q21.31 deletion (patient 28). Other patients with variants in KANSL1 but no craniosynostosis reported.

PMID: 21094706 - Dubourg et al 2011 – report 2 patients with Scaphocephaly and 17q21.31 deletion

PMID: 19447831 -Tan et al 2009 – KANSL1 called KIAA1267 in this paper. Five 17q21.31 deletion patients with phenotypes that include brachycephaly, dolichocephaly, scaphocephaly, positional plagiocephaly.
Created: 16 Apr 2019, 1:33 p.m.
Review on behalf of Tracy Lester and Andrew Wilkie: Zollino report 2 cases with scaphocephaly or sagittal CSS.
Created: 16 Apr 2019, 1:13 p.m.
This region was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Region submitted: KANSL - del (17q21.21); Suggested initial rating: amber
Created: 16 Apr 2019, 1:09 p.m.

Phenotypes
Koolen-de Vries/KANSL haploinsufficiency syndrome.

Details

ISCA ID
ISCA-37420-Loss
ISCA Region Name
17q21.3 recurrent region (includes KANSL1) Loss
Chromosome
17
GRCh38 Coordinates
45608879-46087510
Haploinsufficiency Score
Sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype
Triplosensitivity Score
Required percent of overlap
80%
Sources
  • Expert Review Amber
  • NHS GMS
Phenotypes
  • Koolen-de Vries/KANSL haploinsufficiency syndrome.
Clinvar variants
Variants in
Penetrance
None
Variant types
CNV Loss
Publications

History Filter Activity

14 May 2019, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for Region: ISCA-37420-Loss were changed from to Koolen-de Vries/KANSL haploinsufficiency syndrome.

14 May 2019, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for Region: ISCA-37420-Loss were set to

6 May 2019, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Region: isca-37420-loss has been classified as Amber List (Moderate Evidence).

16 Apr 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Region: ISCA-37420-Loss was added Region: ISCA-37420-Loss was added to Craniosynostosis. Sources: NHS GMS Mode of inheritance for Region: ISCA-37420-Loss was set to