rs80200229
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_004385.5(VCAN):c.6237G>A(p.Lys2079=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 1,614,038 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 36 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 49 hom. )
Consequence
VCAN
NM_004385.5 synonymous
NM_004385.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.130
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 5-83539240-G-A is Benign according to our data. Variant chr5-83539240-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 259372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.13 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1803/152300) while in subpopulation AFR AF= 0.0411 (1707/41546). AF 95% confidence interval is 0.0395. There are 36 homozygotes in gnomad4. There are 857 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1803 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VCAN | NM_004385.5 | c.6237G>A | p.Lys2079= | synonymous_variant | 8/15 | ENST00000265077.8 | |
VCAN-AS1 | NR_136215.1 | n.285-5067C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VCAN | ENST00000265077.8 | c.6237G>A | p.Lys2079= | synonymous_variant | 8/15 | 1 | NM_004385.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0118 AC: 1790AN: 152182Hom.: 35 Cov.: 32
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GnomAD3 exomes AF: 0.00290 AC: 727AN: 250716Hom.: 20 AF XY: 0.00218 AC XY: 296AN XY: 135504
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GnomAD4 exome AF: 0.00126 AC: 1847AN: 1461738Hom.: 49 Cov.: 79 AF XY: 0.00112 AC XY: 814AN XY: 727154
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GnomAD4 genome ? AF: 0.0118 AC: 1803AN: 152300Hom.: 36 Cov.: 32 AF XY: 0.0115 AC XY: 857AN XY: 74464
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Wagner syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Vitreoretinopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at