Variant rs2305562 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.5394+39T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,613,468 control chromosomes in the GnomAD database, including 221,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19234 hom., cov: 31)

Exomes 𝑓: 0.52 ( 202578 hom. )

Consequence

HSPG2
NM_005529.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.67

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=-0.77).

BP6

Variant 1-21857246-A-G is Benign according to our data. Variant chr1-21857246-A-G is described in ClinVar as [Benign]. Clinvar id is 1220862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPG2	NM_005529.7 linkuse as main transcript	c.5394+39T>C		intron_variant		ENST00000374695.8	NP_005520.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPG2	ENST00000374695.8 linkuse as main transcript	c.5394+39T>C		intron_variant		1	NM_005529.7	ENSP00000363827	P1

Frequencies

GnomAD3 genomes

AF:

0.500

AC:

75916

AN:

151812

Hom.:

19217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.428

Gnomad AMI

AF:

0.477

Gnomad AMR

AF:

0.480

Gnomad ASJ

AF:

0.586

Gnomad EAS

AF:

0.459

Gnomad SAS

AF:

0.374

Gnomad FIN

AF:

0.547

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.548

Gnomad OTH

AF:

0.519

GnomAD3 exomes

AF:

0.504

AC:

126636

AN:

251246

Hom.:

32482

AF XY:

0.503

AC XY:

68253

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.420

Gnomad AMR exome

AF:

0.484

Gnomad ASJ exome

AF:

0.588

Gnomad EAS exome

AF:

0.447

Gnomad SAS exome

AF:

0.386

Gnomad FIN exome

AF:

0.551

Gnomad NFE exome

AF:

0.546

Gnomad OTH exome

AF:

0.519

GnomAD4 exome

AF:

0.524

AC:

766130

AN:

1461538

Hom.:

202578

Cov.:

AF XY:

0.522

AC XY:

379589

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.425

Gnomad4 AMR exome

AF:

0.482

Gnomad4 ASJ exome

AF:

0.584

Gnomad4 EAS exome

AF:

0.487

Gnomad4 SAS exome

AF:

0.386

Gnomad4 FIN exome

AF:

0.545

Gnomad4 NFE exome

AF:

0.538

Gnomad4 OTH exome

AF:

0.518

GnomAD4 genome

AF:

0.500

AC:

75984

AN:

151930

Hom.:

19234

Cov.:

AF XY:

0.499

AC XY:

37017

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.428

Gnomad4 AMR

AF:

0.480

Gnomad4 ASJ

AF:

0.586

Gnomad4 EAS

AF:

0.460

Gnomad4 SAS

AF:

0.375

Gnomad4 FIN

AF:

0.547

Gnomad4 NFE

AF:

0.548

Gnomad4 OTH

AF:

0.517

Alfa

AF:

0.544

Hom.:

29113

Bravo

AF:

0.496

Asia WGS

AF:

0.435

AC:

1512

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

-0.77

CADD

Benign

6.9

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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