1-21885751-C-T

Variant names:

• chr1-21885751-C-T
• rs2497632
• NM_005529.7:c.1079-300G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005529.7(HSPG2):​c.1079-300G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,106 control chromosomes in the GnomAD database, including 24,027 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.54 (24027 hom., cov: 33)
• Consequence: HSPG2 NM_005529.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.443

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-21885751-C-T is Benign according to our data. Variant chr1-21885751-C-T is described in ClinVar as [Benign]. Clinvar id is 1229737.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPG2	NM_005529.7	c.1079-300G>A		intron_variant	Intron 9 of 96	ENST00000374695.8	NP_005520.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPG2	ENST00000374695.8	c.1079-300G>A		intron_variant	Intron 9 of 96	1	NM_005529.7	ENSP00000363827.3

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81967 AN: 151988 Hom.: 24016 Cov.: 33

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.578

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.539 AC: 82011 AN: 152106 Hom.: 24027 Cov.: 33 AF XY: 0.538 AC XY: 39964 AN XY: 74340

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.758

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.580

Alfa AF: 0.582 Hom.: 3515

Bravo AF: 0.521

Asia WGS AF: 0.499 AC: 1734 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.078
DANN	Benign	0.48

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

Other links and lift over

dbSNP: rs2497632; hg19: chr1-22212244;