rs142388534
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000393.5(COL5A2):c.249C>T(p.Ala83=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,614,060 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0062 ( 9 hom., cov: 32)
Exomes 𝑓: 0.00084 ( 13 hom. )
Consequence
COL5A2
NM_000393.5 synonymous
NM_000393.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.34
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
Variant 2-189110298-G-A is Benign according to our data. Variant chr2-189110298-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 136962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00622 (946/152194) while in subpopulation AFR AF= 0.0211 (876/41512). AF 95% confidence interval is 0.0199. There are 9 homozygotes in gnomad4. There are 430 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 946 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.249C>T | p.Ala83= | synonymous_variant | 2/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.111C>T | p.Ala37= | synonymous_variant | 5/57 | ||
COL5A2 | XM_047443251.1 | c.111C>T | p.Ala37= | synonymous_variant | 7/59 | ||
COL5A2 | XM_047443252.1 | c.111C>T | p.Ala37= | synonymous_variant | 6/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.249C>T | p.Ala83= | synonymous_variant | 2/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000649966.1 | c.111C>T | p.Ala37= | synonymous_variant | 2/11 | ||||
COL5A2 | ENST00000618828.1 | c.-382C>T | 5_prime_UTR_variant | 2/47 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00621 AC: 945AN: 152076Hom.: 9 Cov.: 32
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GnomAD3 exomes AF: 0.00185 AC: 464AN: 251254Hom.: 4 AF XY: 0.00147 AC XY: 199AN XY: 135786
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GnomAD4 exome AF: 0.000835 AC: 1221AN: 1461866Hom.: 13 Cov.: 33 AF XY: 0.000787 AC XY: 572AN XY: 727236
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GnomAD4 genome ? AF: 0.00622 AC: 946AN: 152194Hom.: 9 Cov.: 32 AF XY: 0.00578 AC XY: 430AN XY: 74402
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 21, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 21, 2013 | 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. - |
Ehlers-Danlos syndrome, classic type, 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 22, 2023 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 25, 2015 | This alteration is classified as 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, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 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