Variant rs2290501 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.7873+25A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,613,542 control chromosomes in the GnomAD database, including 93,940 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11185 hom., cov: 32)

Exomes 𝑓: 0.33 ( 82755 hom. )

Consequence

HSPG2
NM_005529.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.665

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=-0.56).

BP6

Variant 1-21847933-T-G is Benign according to our data. Variant chr1-21847933-T-G is described in ClinVar as [Benign]. Clinvar id is 1256801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-21847933-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPG2	NM_005529.7 linkuse as main transcript	c.7873+25A>C		intron_variant		ENST00000374695.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPG2	ENST00000374695.8 linkuse as main transcript	c.7873+25A>C		intron_variant		1	NM_005529.7	P1
HSPG2	ENST00000453796.1 linkuse as main transcript	n.26A>C		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56142

AN:

151926

Hom.:

11153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.397

Gnomad AMR

AF:

0.268

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.482

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.312

Gnomad OTH

AF:

0.367

GnomAD3 exomes

AF:

0.325

AC:

81523

AN:

250788

Hom.:

14439

AF XY:

0.333

AC XY:

45190

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.525

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.169

Gnomad SAS exome

AF:

0.475

Gnomad FIN exome

AF:

0.329

Gnomad NFE exome

AF:

0.314

Gnomad OTH exome

AF:

0.313

GnomAD4 exome

AF:

0.331

AC:

483107

AN:

1461498

Hom.:

82755

Cov.:

AF XY:

0.334

AC XY:

243072

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.541

Gnomad4 AMR exome

AF:

0.216

Gnomad4 ASJ exome

AF:

0.357

Gnomad4 EAS exome

AF:

0.182

Gnomad4 SAS exome

AF:

0.479

Gnomad4 FIN exome

AF:

0.334

Gnomad4 NFE exome

AF:

0.322

Gnomad4 OTH exome

AF:

0.336

GnomAD4 genome

AF:

0.370

AC:

56229

AN:

152044

Hom.:

11185

Cov.:

AF XY:

0.366

AC XY:

27204

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.526

Gnomad4 AMR

AF:

0.267

Gnomad4 ASJ

AF:

0.350

Gnomad4 EAS

AF:

0.173

Gnomad4 SAS

AF:

0.482

Gnomad4 FIN

AF:

0.334

Gnomad4 NFE

AF:

0.312

Gnomad4 OTH

AF:

0.368

Alfa

AF:

0.327

Hom.:

13607

Bravo

AF:

0.366

Asia WGS

AF:

0.350

AC:

1217

AN:

3478

EpiCase

AF:

0.297

EpiControl

AF:

0.309

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 19, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Lethal Kniest-like syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Schwartz-Jampel syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.0

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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