rs148590409
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2
The NM_000393.5(COL5A2):āc.4173C>Gā(p.Arg1391=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,613,826 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00078 ( 0 hom., cov: 32)
Exomes š: 0.000060 ( 0 hom. )
Consequence
COL5A2
NM_000393.5 synonymous
NM_000393.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.848
Genes affected
COL5A2 (HGNC:2210): (collagen type V alpha 2 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
Variant 2-189035096-G-C is Benign according to our data. Variant chr2-189035096-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 213084.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=3, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=0.848 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000776 (118/152154) while in subpopulation AFR AF= 0.00277 (115/41534). AF 95% confidence interval is 0.00236. There are 0 homozygotes in gnomad4. There are 55 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 118 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.4173C>G | p.Arg1391= | synonymous_variant | 53/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.4035C>G | p.Arg1345= | synonymous_variant | 56/57 | ||
COL5A2 | XM_047443251.1 | c.4035C>G | p.Arg1345= | synonymous_variant | 58/59 | ||
COL5A2 | XM_047443252.1 | c.4035C>G | p.Arg1345= | synonymous_variant | 57/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.4173C>G | p.Arg1391= | synonymous_variant | 53/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000618828.1 | c.3012C>G | p.Arg1004= | synonymous_variant | 46/47 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000776 AC: 118AN: 152036Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000147 AC: 37AN: 251258Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135794
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GnomAD4 exome AF: 0.0000602 AC: 88AN: 1461672Hom.: 0 Cov.: 33 AF XY: 0.0000509 AC XY: 37AN XY: 727144
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GnomAD4 genome ? AF: 0.000776 AC: 118AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.000739 AC XY: 55AN XY: 74380
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Ehlers-Danlos syndrome type 7A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 02, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
COL5A2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 03, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 10, 2015 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Ehlers-Danlos syndrome, classic type, 2 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. - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 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