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Intellectual disability

Gene: ABCC6

Red List (low evidence)

ABCC6 (ATP binding cassette subfamily C member 6)
EnsemblGeneIds (GRCh38): ENSG00000091262
EnsemblGeneIds (GRCh37): ENSG00000091262
OMIM: 603234, Gene2Phenotype
ABCC6 is in 11 panels

5 reviews

Arina Puzriakova (Genomics England Curator)

Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza Stark and Konstantinos Varvagiannis
Created: 14 Aug 2020, 1:58 p.m. | Last Modified: 22 Sep 2020, 3:41 p.m.
Panel Version: 3.330

Zornitza Stark (Australian Genomics)

Red List (low evidence)

GACI and PXE are not typically associated with intellectual disability, dev delay may be secondary to medical complications such as stroke.
Created: 27 Jan 2020, 4:44 a.m. | Last Modified: 27 Jan 2020, 4:44 a.m.
Panel Version: 3.0

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Arterial calcification, generalized, of infancy, 2, MIM#614473; Pseudoxanthoma elasticum, MIM#264800

Konstantinos Varvagiannis (Other)

I don't know

DD/ID is not commonly a feature of ABCC6-related disorders.

PMID: 25392903 is a review on generalized arterial calcification of infancy (GACI). The authors note that the majority of individuals falling into this diagnosis seem to have normal development (although this has not been formally evaluated). For a few patients with severe global developmental delay, this appears to be secondary to strokes or encephalomalacia. Additionaly, as the authors state, eventual motor delay can be explained by joint pain.
PMID: 20301292 is a review on pseudoxanthoma elasticum. DD/ID is not among the features.

In G2P, ABCC6 is a confirmed DD gene associated with GACI. In the publication cited (PMID:22209248) ID was a feature of 2/16 patients reported [table 3 | 1 of these individuals (#14) had a single ABCC6 variant detected].

Intellectual disability is observed in cases of 16p13.11 recurrent microdeletions/duplications which however span several other genes appart from ABCC6. [Microdeletion - https://decipher.sanger.ac.uk/syndrome/79#overview / Microduplication - https://decipher.sanger.ac.uk/syndrome/80#overview].

ABCC6 is not included in gene panels for intellectual disability offered by (several) diagnostic laboratories.

As a result this gene could possibly remain amber or be considered for downgrade to red (low evidence).
Created: 13 Dec 2018, 7:44 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_UKGTN_v12 . Main mutation mechanism : Loss of function
Created: 27 Jul 2017, 4:57 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Louise Daugherty (Genomics England Curator)

Comment on list classification: This gene is from an expert list and needs further assessment by the Genomics England curation team to access inclusion and pertinence to this panel.
Created: 28 Jul 2017, 9:12 a.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
Phenotypes
  • Pseudoxanthoma elasticum, 264800
  • Pseudoxanthoma elasticum, forme fruste, 177850
  • Arterial calcification, generalized, of infancy, 2, 614473
OMIM
603234
Clinvar variants
Variants in ABCC6
Penetrance
Complete
Panels with this gene

History Filter Activity

22 Sep 2020, Gel status: 1

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: abcc6 has been classified as Red List (Low Evidence).

28 Sep 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to ABCC6.

12 Mar 2018, Gel status: 2

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

28 Jul 2017, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

27 Jul 2017, Gel status: 0

Created

BRIDGE consortium (NIHRBR-RD)

ABCC6 was created by BRIDGE

27 Jul 2017, Gel status: 0

Added New Source

BRIDGE consortium (NIHRBR-RD)

ABCC6 was added to Intellectual disabilitypanel. Sources: BRIDGE study SPEED NEURO Tier1 Gene