rs2652106

Variant names:

• chr5-83498217-G-T
• rs2652106
• NM_004385.5:c.748+4286G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004385.5(VCAN):​c.748+4286G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,888 control chromosomes in the GnomAD database, including 12,509 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 0.39 (12509 hom., cov: 32)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709
• Publications: 3 publications found

Genes affected

VCAN (HGNC:2464): (versican) This gene is a member of the aggrecan/versican proteoglycan family. The protein encoded is a large chondroitin sulfate proteoglycan and is a major component of the extracellular matrix. This protein is involved in cell adhesion, proliferation, proliferation, migration and angiogenesis and plays a central role in tissue morphogenesis and maintenance. Mutations in this gene are the cause of Wagner syndrome type 1. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

VCAN Gene-Disease associations (from GenCC):

• Wagner disease

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAN	NM_004385.5	c.748+4286G>T		intron_variant	Intron 5 of 14	ENST00000265077.8	NP_004376.2
VCAN	NM_001164097.2	c.748+4286G>T		intron_variant	Intron 5 of 13		NP_001157569.1
VCAN	NM_001164098.2	c.748+4286G>T		intron_variant	Intron 5 of 13		NP_001157570.1
VCAN	NM_001126336.3	c.748+4286G>T		intron_variant	Intron 5 of 12		NP_001119808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAN	ENST00000265077.8	c.748+4286G>T		intron_variant	Intron 5 of 14	1	NM_004385.5	ENSP00000265077.3

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58779 AN: 151770 Hom.: 12473 Cov.: 32

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.387 AC: 58855 AN: 151888 Hom.: 12509 Cov.: 32 AF XY: 0.389 AC XY: 28879 AN XY: 74222

African (AFR) AF: 0.569 AC: 23534 AN: 41390

American (AMR) AF: 0.300 AC: 4582 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1239 AN: 3466

East Asian (EAS) AF: 0.452 AC: 2328 AN: 5152

South Asian (SAS) AF: 0.389 AC: 1874 AN: 4820

European-Finnish (FIN) AF: 0.354 AC: 3724 AN: 10530

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20373 AN: 67956

Other (OTH) AF: 0.360 AC: 760 AN: 2114

Alfa AF: 0.329 Hom.: 16590

Bravo AF: 0.392

Asia WGS AF: 0.426 AC: 1477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.29
DANN	Benign	0.30
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2652106; hg19: chr5-82794036; COSMIC: COSV54100738;