Severe microcephalyGene: NCAPD2
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review - at least three unrelated pedigrees with the relevant phenotype.
Created: 31 Jul 2020, 3:34 p.m. | Last Modified: 31 Jul 2020, 3:34 p.m.
Panel Version: 2.13
Associated with phenotype in OMIM and a possible gene for Microcephaly with short stature in G2P.
PMID: 27737959 (2016) - A homozygous splice site variant (c.4120+2T>C, p.Asp1374Glyfs*29) in NCAPD2 was detected in a 3-year-old male with severe microcephaly (OFC -11.9 SD), severe ID, autistic-like behaviours, and no speech. The variant was found in a heterozygous state in both unaffected parents and was not present in the ExAC database. Functional studies indicated that the variant disrupted condensin-dependent mitotic chromosome integrity, providing supporting evidence for pathogenicity.
PMID: 28097321 (2017) - In two affected cousins from a consanguineous family with mild ID, intrauterine growth retardation, short stature, and microcephaly. Homozygous missense variants were found in NCAPD2 (c.23T>C, p.Phe8Ser), but also in ENO2 (c.710C>T, p.Thr237Met). Variants segregated with disease in the family, but no further functional studies were undertaken of the variants or patient cells.
PMID: 31056748 (2019) - In a 13-year-old female with severe microcephaly (OFC < -3), mild ID (IQ 59), poor learning performance, sloping forehead and reduced cerebral cortex size, exome sequencing revealed a homozygous variant in NCAPD2 (c.3477+2T>C, p.Gly1160Valfs*16). Progressive microcephaly was also apparent in a sibling of the proband, a male fetus which was terminated at 34 weeks of pregnancy. The same homozygous variant was identified in the fetus, while parents were heterozygotes and an unaffected brother was homozygous for the other allele. No further functional studies of the variant or patient cells were performed.
Created: 31 Jul 2020, 3:33 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Microcephaly 21, primary, autosomal recessive, 617983
Tag for-review tag was added to gene: NCAPD2.
Gene: ncapd2 has been classified as Amber List (Moderate Evidence).
gene: NCAPD2 was added gene: NCAPD2 was added to Severe microcephaly. Sources: Literature Mode of inheritance for gene: NCAPD2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NCAPD2 were set to 27737959; 28097321; 31056748 Phenotypes for gene: NCAPD2 were set to Microcephaly 21, primary, autosomal recessive, 617983 Review for gene: NCAPD2 was set to GREEN