chr2-189064559-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2
The NM_000393.5(COL5A2):c.1714C>T(p.Arg572Trp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000548 in 1,460,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/23 in silico tools predict a damaging outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R572Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_000393.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.1714C>T | p.Arg572Trp | missense_variant, splice_region_variant | 25/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.1576C>T | p.Arg526Trp | missense_variant, splice_region_variant | 28/57 | ||
COL5A2 | XM_047443251.1 | c.1576C>T | p.Arg526Trp | missense_variant, splice_region_variant | 30/59 | ||
COL5A2 | XM_047443252.1 | c.1576C>T | p.Arg526Trp | missense_variant, splice_region_variant | 29/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.1714C>T | p.Arg572Trp | missense_variant, splice_region_variant | 25/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000618828.1 | c.553C>T | p.Arg185Trp | missense_variant, splice_region_variant | 18/47 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251024Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135700
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460138Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726516
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 | Feb 19, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with COL5A2-related disease. This variant is present in population databases (rs768322852, ExAC 0.01%). This sequence change replaces arginine with tryptophan at codon 572 of the COL5A2 protein (p.Arg572Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at