Proteinuric renal disease
Gene: CD2AP
Two unrelated families reported with homozygous variants in this gene reported; mouse model supports pathogenicity, suggest promoting to Amber.Created: 9 Jan 2020, 3:30 a.m. | Last Modified: 9 Jan 2020, 3:30 a.m.
Panel Version: 2.0
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Glomerulosclerosis, focal segmental, 3 #607832
Publications
Associated with Glomerulosclerosis, focal segmental, 3 #607832 in OMIM (no inheritance given)
Mouse knockout model supports renal involvement. 2 cases with heterozgous variants and FSGS but only CD2AP looked at. Two familial cases of homozygous variants (in one only CD2AP screened) and FSGS.
PMID: 10514378 - Shih et al 1999 - In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells.
PMID: 12764198 - Kim et al 2003 - CD2AP+/- showed glomerular abnormalities at 9 months of age but not proteinuria. Screened 30 African-Americans with idiopathic FSGS and 15 African-Americans with HIV-associated FSGS for changes in CD2AP. One variant, predicted to affect the splice acceptor of exon 7 in one allele, was found in 2 patients with primary FSGS and expression of the protein was lower in these patients.
PMID:17713465 - Löwik et al 2007 - report a homozygous variant in a proband with primary Focal segmental glomerulosclerosis, from a consanguineous family of Mediterranean ancestry. A homozygous c1834 C>T (R612Stop) variant was found. Both parents were proven to be heterozygous for this mutation. An immunoblot shows no CD2AP expression in the patient carrying the R612Stop mutation homozygously
PMID: 30612599 - Takano et al 2019 - Using WES, they identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. (Abstract only accessed).Created: 30 Jan 2020, 1:58 p.m. | Last Modified: 30 Jan 2020, 2:26 p.m.
Panel Version: 2.0
This gene was part of an initial gene list collated by Elizabeth Watson, North Bristol NHS Trust, February 2019 on behalf of the GMS Renal Specialist Test Group. Gene Symbol submitted: CD2AP; Suggested initial gene rating: amber; Evidence for inclusion: PMID: 30612599; PMID: 17713465 ; Other comments: Presumed recessive. Reported in multiple unrelated patients, however some of these reported variants now have high MAF. More convincing in two unrelated families: [Full text of PMID:30612599 unavailable, published Jan 2019 - reported hom variant in three affected sibs, not in gnomAD; PMID: 17713465: hom variant in one patient, not in gnomAD]. Reported 3x het VUS in SRNS cohort >600 patients.Created: 4 Feb 2019, 10:41 a.m.
Mode of inheritance
Unknown
Phenotypes
Glomerulosclerosis, focal segmental, 3 #607832
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Only 1 family.Created: 16 May 2016, 8:19 p.m.
Currently on UK diagnostic panel, 2 VUS cases in lab over 300 tested. Listed in several reviews. Reported in literature but pathogenicity not clearly evidenced.Created: 19 Oct 2015, 2:10 p.m.
Mode of inheritance
Unknown
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance for gene: CD2AP was changed from to BIALLELIC, autosomal or pseudoautosomal
Gene: cd2ap has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: CD2AP were changed from to Glomerulosclerosis, focal segmental, 3 #607832
Publications for gene: CD2AP were set to
Source NHS GMS was added to CD2AP.
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
CD2AP was added to Proteinuric renal diseasepanel. Source: Eligibility statement prior genetic testing
CD2AP was added to Proteinuric renal diseasepanel. Sources: Eligibility statement prior genetic testing