rs10799719
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_005529.7(HSPG2):c.63+14767C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 152,038 control chromosomes in the GnomAD database, including 22,531 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.54 ( 22531 hom., cov: 33)
Consequence
HSPG2
NM_005529.7 intron
NM_005529.7 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.41
Publications
8 publications found
Genes affected
HSPG2 (HGNC:5273): (heparan sulfate proteoglycan 2) This gene encodes the perlecan protein, which consists of a core protein to which three long chains of glycosaminoglycans (heparan sulfate or chondroitin sulfate) are attached. The perlecan protein is a large multidomain proteoglycan that binds to and cross-links many extracellular matrix components and cell-surface molecules. It has been shown that this protein interacts with laminin, prolargin, collagen type IV, FGFBP1, FBLN2, FGF7 and transthyretin, etc., and it plays essential roles in multiple biological activities. Perlecan is a key component of the vascular extracellular matrix, where it helps to maintain the endothelial barrier function. It is a potent inhibitor of smooth muscle cell proliferation and is thus thought to help maintain vascular homeostasis. It can also promote growth factor (e.g., FGF2) activity and thus stimulate endothelial growth and re-generation. It is a major component of basement membranes, where it is involved in the stabilization of other molecules as well as being involved with glomerular permeability to macromolecules and cell adhesion. Mutations in this gene cause Schwartz-Jampel syndrome type 1, Silverman-Handmaker type of dyssegmental dysplasia, and tardive dyskinesia. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]
HSPG2 Gene-Disease associations (from GenCC):
- Schwartz-Jampel syndrome type 1Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
- Silverman-Handmaker type dyssegmental dysplasiaInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
- Schwartz-Jampel syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.535 AC: 81333AN: 151920Hom.: 22512 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
81333
AN:
151920
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.535 AC: 81397AN: 152038Hom.: 22531 Cov.: 33 AF XY: 0.534 AC XY: 39675AN XY: 74328 show subpopulations
GnomAD4 genome
AF:
AC:
81397
AN:
152038
Hom.:
Cov.:
33
AF XY:
AC XY:
39675
AN XY:
74328
show subpopulations
African (AFR)
AF:
AC:
17353
AN:
41452
American (AMR)
AF:
AC:
7637
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
AC:
2524
AN:
3472
East Asian (EAS)
AF:
AC:
1740
AN:
5168
South Asian (SAS)
AF:
AC:
2783
AN:
4826
European-Finnish (FIN)
AF:
AC:
5622
AN:
10574
Middle Eastern (MID)
AF:
AC:
197
AN:
292
European-Non Finnish (NFE)
AF:
AC:
41904
AN:
67956
Other (OTH)
AF:
AC:
1204
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1891
3782
5672
7563
9454
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1709
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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