rs371259794
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_000393.5(COL5A2):c.4307A>G(p.Glu1436Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E1436E) has been classified as Likely benign.
Frequency
Consequence
NM_000393.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.4307A>G | p.Glu1436Gly | missense_variant | 53/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.4169A>G | p.Glu1390Gly | missense_variant | 56/57 | ||
COL5A2 | XM_047443251.1 | c.4169A>G | p.Glu1390Gly | missense_variant | 58/59 | ||
COL5A2 | XM_047443252.1 | c.4169A>G | p.Glu1390Gly | missense_variant | 57/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.4307A>G | p.Glu1436Gly | missense_variant | 53/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000618828.1 | c.3146A>G | p.Glu1049Gly | missense_variant | 46/47 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250996Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135640
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461628Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727110
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, classic type, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 24, 2016 | This variant is present in population databases (rs371259794, ExAC 0.004%) but has not been reported in the literature in individuals with a COL5A2-related disease. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This sequence change replaces glutamic acid with glycine at codon 1436 of the COL5A2 protein (p.Glu1436Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at