rs117085226
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000393.5(COL5A2):c.403-16T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,276 control chromosomes in the GnomAD database, including 563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.015 ( 44 hom., cov: 32)
Exomes 𝑓: 0.0097 ( 519 hom. )
Consequence
COL5A2
NM_000393.5 splice_polypyrimidine_tract, intron
NM_000393.5 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.417
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=-0.56).
BP6
?
Variant 2-189097346-A-T is Benign according to our data. Variant chr2-189097346-A-T is described in ClinVar as [Benign]. Clinvar id is 136969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-189097346-A-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.073 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.403-16T>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000374866.9 | |||
COL5A2 | XM_011510573.4 | c.265-16T>A | splice_polypyrimidine_tract_variant, intron_variant | ||||
COL5A2 | XM_047443251.1 | c.265-16T>A | splice_polypyrimidine_tract_variant, intron_variant | ||||
COL5A2 | XM_047443252.1 | c.265-16T>A | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.403-16T>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000393.5 | P1 | |||
COL5A2 | ENST00000618828.1 | c.-228-16T>A | splice_polypyrimidine_tract_variant, intron_variant | 5 | |||||
COL5A2 | ENST00000649966.1 | c.265-16T>A | splice_polypyrimidine_tract_variant, intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0147 AC: 2240AN: 152144Hom.: 41 Cov.: 32
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GnomAD3 exomes AF: 0.0222 AC: 5590AN: 251380Hom.: 184 AF XY: 0.0239 AC XY: 3246AN XY: 135862
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GnomAD4 exome AF: 0.00970 AC: 14167AN: 1461014Hom.: 519 Cov.: 30 AF XY: 0.0116 AC XY: 8439AN XY: 726868
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GnomAD4 genome ? AF: 0.0148 AC: 2251AN: 152262Hom.: 44 Cov.: 32 AF XY: 0.0163 AC XY: 1212AN XY: 74446
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 14, 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 16, 2017 | Variant summary: The COL5A2 c.403-16T>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant of interest has been observed in a large, broad control population, ExAC, in 2692/120714 control chromosomes (91 homozygotes) at a frequency of 0.0223006, which is approximately 3568 times the estimated maximal expected allele frequency of a pathogenic COL5A2 variant (0.0000063), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. - |
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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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