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Intellectual disability syndromic and non-syndromic

Gene: CAPZA2

Green List (high evidence)

CAPZA2 (capping actin protein of muscle Z-line alpha subunit 2)
EnsemblGeneIds (GRCh38): ENSG00000198898
EnsemblGeneIds (GRCh37): ENSG00000198898
OMIM: 601571, Gene2Phenotype
CAPZA2 is in 2 panels

2 reviews

Chris Ciotta (Victorian Clinical Genetics Services)

Green List (high evidence)

Now 4 unrelated families in the literature, Huang et al. (2020) identified two de novo missense variants, Pi (2022) in a letter to the editor identified a de novo in-frame del of Arg260 in an individual with seizures, hypotonia and developmental delay. Zhang et al. (2024) most recently identified a de novo canonical splice variant shown by RT-PCR to create exon skipping and an NMD-predicted frameshift. This individual presented with seizures and was later diagnosed with intellectual disability and mild motor delay.

All 4 individuals had seizures, 3/4 had speech delay and motor delay, 1/4 had microcephaly.

Disease mechanism not established, Loss of function and DN has been suggested. LoF variants in gnomad with over 1 het have poor quality and gene has a pLI score of 0.98.
Created: 8 Dec 2024, 11:59 p.m. | Last Modified: 8 Dec 2024, 11:59 p.m.
Panel Version: 1.19

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

Phenotypes
Neurodevelopmental disorder, MONDO:0700092, CAPZA2-related

Publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

I don't know

PMID: 32338762 - Huang et al 2020 - report 2 unrelated families (Chinese and European) in which a de novo heterozygous variant has been identified in CAPZA2 in paediatric probands that present with global motor development delay, speech delay, intellectual disability, hypotonia. One proband had seizures at 7 months but these were controlled with medication and did not repeat. The other proband at age one had an atypical febrile seizure that was controlled without medication. Functional studies in Drosophila suggest that these variants are mild loss of function mutations but that they can act as dominant negative variants in actin polymerization in bristles.
Sources: Literature
Created: 2 Jul 2020, 10:21 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual disability

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Neurodevelopmental disorder, MONDO:0700092, CAPZA2-related
OMIM
601571
Clinvar variants
Variants in CAPZA2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

9 Dec 2024, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: CAPZA2 were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, CAPZA2-related

9 Dec 2024, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: CAPZA2 were set to 32338762

9 Dec 2024, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: capza2 has been classified as Green List (High Evidence).

2 Jul 2020, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: capza2 has been classified as Amber List (Moderate Evidence).

2 Jul 2020, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: capza2 has been classified as Amber List (Moderate Evidence).

2 Jul 2020, Gel status: 1

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

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: CAPZA2 was added gene: CAPZA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: CAPZA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CAPZA2 were set to 32338762 Phenotypes for gene: CAPZA2 were set to Intellectual disability Review for gene: CAPZA2 was set to AMBER