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Rare syndromic craniosynostosis or isolated multisuture synostosis

Region: ISCA-37420-Loss

17q21.3 recurrent region (includes KANSL1) Loss

Amber List (moderate evidence)
Chromosome: 17
GRCh38 Position: 45627800-46087514
Haploinsufficiency Score: Sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype
Triplosensitivity Score:
Required percent of overlap: 60%
Variant types: CNV Loss

2 reviews

Arina Puzriakova (Genomics England Curator)

The required percent of overlap for this region has been changed from 80% to 60% and the genomic location has been updated inline with ClinGen following NHS Genomic Medicine Service approval.
Created: 16 Mar 2022, 1:01 p.m. | Last Modified: 16 Mar 2022, 1:01 p.m.
Panel Version: 2.67
Created: 16 Mar 2022, 1:01 p.m.
Last Modified: 16 Mar 2022, 1:01 p.m.
Panel version: 2.67

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.

Created: 16 Apr 2019, 1:09 p.m.

Panel version: 1.133

Details

ISCA ID
ISCA-37420-Loss
ISCA Region Name
17q21.3 recurrent region (includes KANSL1) Loss
Chromosome
17
GRCh38 Coordinates
45627800-46087514
Haploinsufficiency Score
Sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype
Triplosensitivity Score
Required percent of overlap
60%
Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • NHS GMS
Phenotypes
  • Koolen-De Vries syndrome, OMIM:610443
  • Developmental delay/intellectual disability, hypotonia, distinctive facial features, congenital malformations, and behavioural feature
Clinvar variants
Variants in
Penetrance
None
Variant types
CNV Loss
Publications

History Filter Activity

7 Feb 2023, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for Region: ISCA-37420-Loss were changed from Koolen-de Vries/KANSL haploinsufficiency syndrome. to Koolen-De Vries syndrome, OMIM:610443; Developmental delay/intellectual disability, hypotonia, distinctive facial features, congenital malformations, and behavioural feature

16 Mar 2022, Gel status: 2

Changed GRCh38, Changed Required Overlap Percentage

Arina Puzriakova (Genomics England Curator)

GRCh38 position for ISCA-37420-Loss was changed from 45608879-46087510 to 45627800-46087514. Required Overlap Percentage for ISCA-37420-Loss was changed from 80 to 60.

7 May 2020, Gel status: 2

Set mode of inheritance

Catherine Snow (Genomics England)

Mode of inheritance for Region: ISCA-37420-Loss was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

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