DCHS1
  • 1
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
DCHS1 (HGNC:13681) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
dachsous cadherin-related 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
CDH25, PCDH16
Alias symbols
FIB1, KIAA1773, FLJ11790, CDHR6
%HI
44.76(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.32(Read more about gnomAD pLI score)
LOEUF
0.49(Read more about gnomAD LOEUF score)
Cytoband
11p15.4
Genomic Coordinates
GRCh37/hg19: chr11:6642561-6677040 NCBI Ensembl UCSC
GRCh38/hg38: chr11:6621330-6655809 NCBI Ensembl UCSC
MANE Select Transcript
NM_003737.4 ENST00000299441.5 (Read more about MANE Select)
Function
Calcium-dependent cell-adhesion protein. Mediates functions in neuroprogenitor cell proliferation and differentiation. In the heart, has a critical role for proper morphogenesis of the mitral valve, acting in the regulation of cell migration involved in valve formation (PubMed:26258302). {ECO:0000269|PubMed:26258302}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-10049
ClinGen Curation ID:
CCID:006974
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency (1)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
08/31/2018

Haploinsufficiency (HI) Score Details

HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency (Disclaimer)
HI Evidence:
  • PUBMED: 26258302
    Durst et al (2015) describe pathogenic variants in DCHS1 identified in families with non-syndormic mitral valve prolapse (MVP). Linkage analysis of the first family previously identified in Freed et al (PMID: 12707861) demonstrated a candidate region for MVP at 11p15.4. Four affected individuals from this family were sequenced within the target region, and all demonstrated a compound heterozygous missense variants in DCSH1 in cis, p.P197L and p.R2513H, segregating with the phenotype. Western blots from transfected constructs created with individual p.P197L and p.R2513H variants demonstrated the p.R2513H variant resulted in reduced protein levels, consistent with loss-of-function. Two additional MVP families were identified by exome sequencing, both of which had the same heterozygous missense variant, c.6988C>T (p.R2330C) segregating with the phenotype. Western blot analyses demonstrated an apparent loss of function mechanism for this variant.
HI Evidence Comments:
PMID: 29224215 Clemenceau et al evaluated 100 asymptomatic subjects with MVP and mitral valve regurgitation for the specific variants in DCHS1 reported by Durst et al. None of the 100 had either variant. However, two of the 100 subjects were found to have predicted pathogenic missense variants in exon 21: p.R2462Q and p.A2464P. Further sequencing of all 21 exons and the UTRs in 12 randomly selected subjects revealed potentially 4 additional deleterious missense variants (p.S415R, p.R2827P, p.A2867T, and p.R2770Q), which were then used for targeted screening in the remaining 88 subjects. In total, 24/100 subjects were identified with a likely pathogenic missense variant. The authors acknowledge that other variants not targeted may be present in the 88 subjects who were not fully sequenced. No functional studies were performed to determine the mechanism of pathogenicity of any variant in the study. Based on a lack of focal copy number changes in the literature and only one report with functional studies demonstrating possible haploinsufficiency, the current score for haploinsufficiency is 1.

Triplosensitivity (TS) Score Details

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

Genomic View

Select assembly: (NC_000011.9) (NC_000011.10)