• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
MEIS2 (HGNC:7001) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
Meis homeobox 2
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
MRG1, HsT18361
%HI
0.69(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.18(Read more about gnomAD LOEUF score)
Cytoband
15q14
Genomic Coordinates
GRCh37/hg19: chr15:37181405-37393512 NCBI Ensembl UCSC
GRCh38/hg38: chr15:36889204-37101311 NCBI Ensembl UCSC
MANE Select Transcript
NM_170675.5 ENST00000561208.6 (Read more about MANE Select)
Function
Involved in transcriptional regulation. Binds to HOX or PBX proteins to form dimers, or to a DNA-bound dimer of PBX and HOX proteins and thought to have a role in stabilization of the homeoprotein-DNA complex. Isoform 3 is required for the activity of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer ... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-29844
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
09/14/2021

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies Monarch
HI Evidence:
  • PUBMED: 30291340
    Verheije et al. (2019) report nine patients with de novo sequence variants in the MEIS2 gene, identified by WES (N = 8) or Sanger sequencing (N = 1). The variants identified included two nonsense variants, c.978G>A (p.Trp326*) and c.829C>T (p.Gln277*); three frameshift variants, c.868dup (p.Ile290Asnfs*40), c.383del (p.Lys128Serfs*19), and c.934_937del (p.Leu312Argfs*11); three canonical splice site variants, c.639+1G>A, c.640-2A>G, and c.978-2A>G; and one missense variant, c.998G>A (p.Arg333Lys). All nonsense, frameshift, and splice site variants occurred upstream of the penultimate exon. All nine patients presented with varying degrees of intellectual disability. Palatal defects were present in 7/8 patients that were assessed, and ranged from bifid uvula to cleft palate. Heart defects were present in 5 of 9 patients. No recognizable facial gestalt was present, but the authors identified thin, arched eyebrows, bitemporal narrowing, hypoplastic alae nasi, and a thin upper lip as recurrent facial features. The authors identified 15 additional patients with deletions ranging from 0.19-6.97 Mb that included MEIS2. All patients with CNVs had intellectual disability or developmental delay, palatal defects were present in 10/14, and congenital heart defects were present in 5/13.
  • PUBMED: 30735726
    Giliberti et al. (2020) report a de novo nonsense variant, c.520C>T (p.R174*), in exon 6 of MEIS2 in a male who underwent trio WES analysis at age 10 due to intellectual disability. Cleft lip/palate was not present. He had a history of ventricular and atrial septal defect, psychomotor delay, and undescended right testicle. Dysmorphic features included large forehead, low frontal hairline, thick hair, thin and laterally extended eyebrows, large nasal tip with anteverted and hypoplastic nostrils, M-shaped upper lip, high palate, tapering fingers, and sandal gap bilaterally. His IQ was 45, and he was diagnosed with autism spectrum disorder. Brain MRI detected ectasia and gliosis of Virchow-Robin areas.
  • PUBMED: 27225850
    Fujita et al. (2016) identified a de novo nonsense variant, c.611C>G (p.S204*), in exon 6 of MEIS2 in a female who underwent singleton WES analysis (parentage confirmed using nine microsatellite markers). She presented with cleft palate, atrial septal defect (ASD), and ventricular septal defect (VSD) at birth. Other clinical features included motor and speech delay, severe gastroesophageal reflux requiring gastronomy, and dysmorphic features that included large forehead, mild trigonocephaly, sparse eyebrow, deeply set eyes, large and low-set ears, full cheeks, and thin upper lip vermilion.
  • PUBMED: 28934986
    Gambin et al. (2017) retrospectively analyzed data from 63,127 patients referred for clinical chromosomal microarray analysis (CMA) at Baylor Genetics laboratories. They identified a de novo 3.2 kb deletion encompassing exon 8 of MEIS2 in male patient who was referred for cleft palate and possible verbal developmental delay. The deletion was confirmed by PCR and Sanger sequencing (Sanger coordinates - chr15:37,328,986-37,332,249). Parental studies were performed using CMA. Larger deletions encompassing MEIS2 and additional genes were identified in five patients.
  • PUBMED: 20425846
    Crowley et al. (2010) report a male infant born with cleft palate, ventricular septal defect, and bilateral hearing loss who had a de novo mosaic 123 kilobase deletion of exon 9 on the MEIS2 gene. This deletion was predicted to result in a frameshift and truncated protein. The deletion was estimated to be present in about 40% of cells.
  • PUBMED: 24678003
    Johansson et al. (2014) report three siblings and their mother who had cleft palate, delayed motor skills, and intellectual disability. They were all found to carry a 58 kilobase intragenic tandem duplication which was predicted to result in a frameshift. The duplication occurred de novo in the mother. The authors also report individuals from four other families with deletions ranging from 0.6-4.8 Mb that include MEIS2. All of these individuals had cleft palate, all but one had intellectual disability and delayed motor skills, one had a cleft lip, and three had ventricular septal defects.
HI Evidence Comments:
Numerous individuals with de novo loss-of-function variants in MEIS2 have been identified, with common features that include intellectual disability, delayed motor development, orofacial clefting, and/or cardiac malformations. Non-focal deletions (1.6-5.6 Mb) encompassing MEIS2 and additional genes that have been identified in patients with similar clinical findings (PMIDs: 17163532, 18458017, 21504564; summarized in PMID: 30291340). Based on the evidence above, the haploinsufficiency score is a 3.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000015.9) (NC_000015.10)