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Severe microcephaly

Gene: NCAPD2

Amber List (moderate evidence)

NCAPD2 (non-SMC condensin I complex subunit D2)
EnsemblGeneIds (GRCh38): ENSG00000010292
EnsemblGeneIds (GRCh37): ENSG00000010292
OMIM: 615638, Gene2Phenotype
NCAPD2 is in 3 panels

1 review

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

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.
Sources: Literature
Created: 31 Jul 2020, 3:33 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Microcephaly 21, primary, autosomal recessive, 617983

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Microcephaly 21, primary, autosomal recessive, 617983
Tags
for-review
OMIM
615638
Clinvar variants
Variants in NCAPD2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

31 Jul 2020, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: NCAPD2.

31 Jul 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: ncapd2 has been classified as Amber List (Moderate Evidence).

31 Jul 2020, Gel status: 1

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

Arina Puzriakova (Genomics England Curator)

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