| Geno
|
Mag
|
Summary
|
| (A;A)
|
1.1
|
likely to be a benign variant
|
| (A;G)
|
1
|
likely to be a benign variant
|
| (G;G)
|
0
|
common in clinvar
|
rs61735045, also known as c.1588G>A, p.Gly530Ser and G530S, is a variant in the COL5A1 gene on chromosome 9.
Two papers published in 2000 and 2002 proposed that carrying one copy of an rs61735045(A) allele worsened symptoms of Ehlers-Danlos syndrome(EDS) in those who had it due to a causative mutation elsewhere, and that carrying two copies would cause EDS.[PMID 10602121] [PMID 11992482]
More recent analyses have concluded that the rs61735045(A) allele is quite likely to actually be benign. A 2009 publication found that the frequency of the 530S allele was similar (about 5%) in all groups of people they studied, whether healthy or EDS-affected. Furthermore, the predicted homozygote minor frequency of 1 in 400 people is much higher than that of classical EDS.[PMID 19370768
] More recently, ExAC analysis shows an allele frequency of 3.5%, and a minor homozygote frequency of about 1 in 1000, which is still an order of magnitude or more higher than the estimated EDS incidence, incidating that either this allele is benign or the penetrance of even a double mutation is quite low.
Additionally, as of 2014, two labs are reporting in ClinVar this variant as benign.
In summary, the majority of current evidence indicates that the rs61735045 variant is likely to be benign.
[PMID 10602121] Compound heterozygosity for a disease-causing G1489E [correction of G1489D] and disease-modifying G530S substitution in COL5A1 of a patient with the classical type of Ehlers-Danlos syndrome: an explanation of intrafamilial variability?
[PMID 11992482] Homozygous Gly530Ser substitution in COL5A1 causes mild classical Ehlers-Danlos syndrome.
] More recently, ExAC analysis shows an allele frequency of 3.5%, and a minor homozygote frequency of about 1 in 1000, which is still an order of magnitude or more higher than the estimated EDS incidence, incidating that either this allele is benign or the penetrance of even a double mutation is quite low.
