chr2-189098740-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_000393.5(COL5A2):c.389G>A(p.Arg130His) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,612,780 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R130C) has been classified as Uncertain significance.
Frequency
Consequence
NM_000393.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.389G>A | p.Arg130His | missense_variant | 5/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.251G>A | p.Arg84His | missense_variant | 8/57 | ||
COL5A2 | XM_047443251.1 | c.251G>A | p.Arg84His | missense_variant | 10/59 | ||
COL5A2 | XM_047443252.1 | c.251G>A | p.Arg84His | missense_variant | 9/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.389G>A | p.Arg130His | missense_variant | 5/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000649966.1 | c.251G>A | p.Arg84His | missense_variant | 5/11 | ||||
COL5A2 | ENST00000618828.1 | c.-242G>A | 5_prime_UTR_variant | 5/47 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152126Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251290Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135834
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1460654Hom.: 0 Cov.: 29 AF XY: 0.00000963 AC XY: 7AN XY: 726702
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152126Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6AN XY: 74302
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 03, 2021 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; Not located in the triple helical region, where the majority of pathogenic missense variants occur (Symoens et al., 2012; Stenson et al., 2014); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 425252; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 23587214, 11006503, 22696272, 8168810) - |
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 06, 2020 | The p.R130H variant (also known as c.389G>A), located in coding exon 5 of the COL5A2 gene, results from a G to A substitution at nucleotide position 389. The arginine at codon 130 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Ehlers-Danlos syndrome, classic type, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | COL5A2 NM_000393.4 exon 5 p.Arg130His (c.389G>A): This variant has not been reported in the literature but is present in 0.01% (4/24956) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/2-189963466-C-T). This variant is present in ClinVar (Variation ID:425252). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Ehlers-Danlos syndrome, classic type Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Oct 02, 2019 | COL5A2 NM_000393.4 exon 5 p.Arg130His (c.389G>A): This variant has not been reported in the literature but is present in 0.01% (4/24956) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/2-189963466-C-T). This variant is present in ClinVar (Variation ID:425252). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at