rs121912930
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PP2PP3_StrongPP5_Moderate
The NM_000393.5(COL5A2):c.3445G>C(p.Gly1149Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G1149G) 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_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.3445G>C | p.Gly1149Arg | missense_variant | 48/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.3307G>C | p.Gly1103Arg | missense_variant | 51/57 | ||
COL5A2 | XM_047443251.1 | c.3307G>C | p.Gly1103Arg | missense_variant | 53/59 | ||
COL5A2 | XM_047443252.1 | c.3307G>C | p.Gly1103Arg | missense_variant | 52/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.3445G>C | p.Gly1149Arg | missense_variant | 48/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000618828.1 | c.2284G>C | p.Gly762Arg | missense_variant | 41/47 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, classic type Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 1998 | - - |
Ehlers-Danlos syndrome, classic type, 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 13, 2022 | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL5A2 protein function. ClinVar contains an entry for this variant (Variation ID: 17198). This missense change has been observed in individual(s) with Ehlers-Danlos syndrome (PMID: 9783710). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs121912930, gnomAD 0.0009%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1149 of the COL5A2 protein (p.Gly1149Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at