rs371259794
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_000393.5(COL5A2):āc.4307A>Gā(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 (ā ). 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