rs781014698

Variant names:

• chr5-83483574-A-C
• rs781014698
• ENST00000512590.6:c.-89A>C

Your query was ambiguous. Multiple possible variants found:

• chr5-83483574-A-C
• chr5-83483574-A-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The ENST00000512590.6(VCAN):​c.-89A>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,461,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: VCAN ENST00000512590.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72
• Publications: 1 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: G2P, Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.42152026).
• BS2: High AC in GnomAdExome4 at 16 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000512590.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	NM_004385.5	MANE Select	c.56A>C	p.His19Pro	missense	Exon 2 of 15	NP_004376.2
	VCAN	NM_001164097.2		c.56A>C	p.His19Pro	missense	Exon 2 of 14	NP_001157569.1	P13611-2
	VCAN	NM_001164098.2		c.56A>C	p.His19Pro	missense	Exon 2 of 14	NP_001157570.1	P13611-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	ENST00000512590.6	TSL:1	c.-89A>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 14	ENSP00000425959.2	E9PF17
	VCAN	ENST00000265077.8	TSL:1 MANE Select	c.56A>C	p.His19Pro	missense	Exon 2 of 15	ENSP00000265077.3	P13611-1
	VCAN	ENST00000343200.9	TSL:1	c.56A>C	p.His19Pro	missense	Exon 2 of 14	ENSP00000340062.5	P13611-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251178 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1461076 Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7 AN XY: 726864

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39584

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111502

Other (OTH) AF: 0.00 AC: 0 AN: 60358

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.095
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.42	T
MetaSVM	Uncertain	-0.086	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.7
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.027	D
Polyphen		0.98	D
Vest4		0.60
MutPred		0.50		Gain of helix (P = 0.062)
MVP		0.74
MPC		0.35
ClinPred		0.93	D
GERP RS		4.3
Varity_R		0.33
gMVP		0.46
Mutation Taster		=81/19	polymorphism

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: rs781014698; hg19: chr5-82779393;