rs141210030
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PP2PP3BP4BP6BS2
The NM_000393.5(COL5A2):āc.2492G>Cā(p.Gly831Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000886 in 1,613,518 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). Synonymous variant affecting the same amino acid position (i.e. G831G) has been classified as Likely benign.
Frequency
Consequence
NM_000393.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.2492G>C | p.Gly831Ala | missense_variant | 37/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.2354G>C | p.Gly785Ala | missense_variant | 40/57 | ||
COL5A2 | XM_047443251.1 | c.2354G>C | p.Gly785Ala | missense_variant | 42/59 | ||
COL5A2 | XM_047443252.1 | c.2354G>C | p.Gly785Ala | missense_variant | 41/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.2492G>C | p.Gly831Ala | missense_variant | 37/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000618828.1 | c.1331G>C | p.Gly444Ala | missense_variant | 30/47 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000355 AC: 54AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000996 AC: 25AN: 250992Hom.: 0 AF XY: 0.0000811 AC XY: 11AN XY: 135688
GnomAD4 exome AF: 0.0000602 AC: 88AN: 1461300Hom.: 0 Cov.: 31 AF XY: 0.0000564 AC XY: 41AN XY: 727004
GnomAD4 genome ? AF: 0.000361 AC: 55AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28AN XY: 74436
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jun 16, 2023 | BS1, PP3, PM1 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 08, 2021 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar (ClinVar Variant ID# 255998; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 22696272, 24077912) - |
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 23, 2023 | The p.G831A variant (also known as c.2492G>C), located in coding exon 37 of the COL5A2 gene, results from a G to C substitution at nucleotide position 2492. The glycine at codon 831 is replaced by alanine, an amino acid with similar properties. Internal structural analysis indicates that this alteration disrupts the characteristic G-X-Y motif of the triple helical domain in the COL5A2 protein and inserts a bulky side chain into a sterically-constrained region (Bella J et al. Science. 1994;266:75-81; Hohenester E et al. Proc. Natl. Acad. Sci.U.S.A. 2008;105:18273-7; Ambry internal data). Glycine substitutions in the triple helical domain of COL5A2 have been reported in association with classic Ehlers-Danlos syndrome (cEDS), but the number of affected individuals is limited and several other COL5A2 glycine substitutions in the triple helical domain (e.g., p.G951E and p.G831A) are too common for disease in population databases (Symoens S et al. Hum. Mutat., 2012 Oct;33:1485-93; Ritelli M et al. Orphanet J Rare Dis. 2013 Apr;8:58). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 09, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at