PhenoModifier-Variant Detail

Variant "COL5A1:c.2852A>G(p.Asn951Ser)"

Search result: 1 record

Variant information

Gene:

COL5A1

Variant:

COL5A1:c.2852A>G(p.Asn951Ser)

Genomic location:

chr9:137688701(hg19)

HGVS:

SO Term	RefSeq
protein_coding	NM_000093.4:c.2852A>G(p.Asn951Ser)
protein_coding	NM_001278074.1:c.2852A>G(p.Asn951Ser)

dbSNP ID:

rs61736966

GWAS trait:

no data

Modifier statisitcs

Record:

1

Disorder:

1

Reference:

1

Effect type:

Expressivity(1)

Modifier effect:

Altered severity(1)

Detail：

Target disease:

Thoracic Aortic Aneurysm (DOID_14004)

Effect type:

Expressivity

Modifier effect:

Altered severity

Evidence:

Pedigree analysis and gene activity study

Effect:

Genetic modifiers of TAA severity

Reference:

PMID28550590

Title:

Exome Sequencing Identifies Candidate Genetic Modifiers of Syndromic and Familial Thoracic Aortic Aneurysm Severity.

Species studied:

Human

Abstract:

Thoracic aortic aneurysm (TAA) is a genetic disease predisposing to aortic dissection. It is important to identify the genetic modifiers controlling penetrance and expressivity to improve clinical prognostication. Exome sequencing was performed in 27 subjects with syndromic or familial TAA presenting with extreme phenotypes (15 with severe TAA; 12 with mild or absent TAA). Family-based analysis of a subset of the cohort identified variants, genes, and pathways segregating with TAA severity among three families. A rare missense variant in ADCK4 (p.Arg63Trp) segregated with mild TAA in each family. Genes and pathways identified in families were further investigated in the entire cohort using the optimal unified sequence kernel association test, finding significance for the gene COL15A1 (p = 0.025) and the retina homeostasis pathway (p = 0.035). Thus, we identified candidate genetic modifiers of TAA severity by exome-based study of extreme phenotypes, which may lead to improved risk stratification and development of new medical therapies.