Variant rs7355045 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005529.7(HSPG2):c.8464+143A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 979,460 control chromosomes in the GnomAD database, including 317,727 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 46024 hom., cov: 32)

Exomes 𝑓: 0.81 ( 271703 hom. )

Consequence

HSPG2
NM_005529.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.41

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-21845965-T-C is Benign according to our data. Variant chr1-21845965-T-C is described in ClinVar as [Benign]. Clinvar id is 1245045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPG2	NM_005529.7 link	c.8464+143A>G		intron_variant		ENST00000374695.8	NP_005520.4	P98160

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPG2	ENST00000374695.8 link	c.8464+143A>G		intron_variant		1	NM_005529.7	ENSP00000363827.3		P98160

Frequencies

GnomAD3 genomes

AF:

0.775

AC:

117918

AN:

152070

Hom.:

45976

Cov.:

show subpopulations

Gnomad AFR

AF:

0.700

Gnomad AMI

AF:

0.807

Gnomad AMR

AF:

0.709

Gnomad ASJ

AF:

0.894

Gnomad EAS

AF:

0.821

Gnomad SAS

AF:

0.821

Gnomad FIN

AF:

0.824

Gnomad MID

AF:

0.829

Gnomad NFE

AF:

0.815

Gnomad OTH

AF:

0.789

GnomAD4 exome

AF:

0.809

AC:

669565

AN:

827274

Hom.:

271703

AF XY:

0.812

AC XY:

347087

AN XY:

427708

show subpopulations

Gnomad4 AFR exome

AF:

0.707

Gnomad4 AMR exome

AF:

0.694

Gnomad4 ASJ exome

AF:

0.891

Gnomad4 EAS exome

AF:

0.839

Gnomad4 SAS exome

AF:

0.812

Gnomad4 FIN exome

AF:

0.816

Gnomad4 NFE exome

AF:

0.815

Gnomad4 OTH exome

AF:

0.807

GnomAD4 genome

AF:

0.776

AC:

118021

AN:

152186

Hom.:

46024

Cov.:

AF XY:

0.774

AC XY:

57595

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.701

Gnomad4 AMR

AF:

0.709

Gnomad4 ASJ

AF:

0.894

Gnomad4 EAS

AF:

0.821

Gnomad4 SAS

AF:

0.821

Gnomad4 FIN

AF:

0.824

Gnomad4 NFE

AF:

0.815

Gnomad4 OTH

AF:

0.789

Alfa

AF:

0.796

Hom.:

6001

Bravo

AF:

0.766

Asia WGS

AF:

0.828

AC:

2877

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.7

DANN

Benign

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over