2-189035106-G-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_000393.5(COL5A2):c.4163C>G(p.Thr1388Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,722 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000393.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.4163C>G | p.Thr1388Ser | missense_variant | Exon 53 of 54 | ENST00000374866.9 | NP_000384.2 | |
COL5A2 | XM_011510573.4 | c.4025C>G | p.Thr1342Ser | missense_variant | Exon 56 of 57 | XP_011508875.1 | ||
COL5A2 | XM_047443251.1 | c.4025C>G | p.Thr1342Ser | missense_variant | Exon 58 of 59 | XP_047299207.1 | ||
COL5A2 | XM_047443252.1 | c.4025C>G | p.Thr1342Ser | missense_variant | Exon 57 of 58 | XP_047299208.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.4163C>G | p.Thr1388Ser | missense_variant | Exon 53 of 54 | 1 | NM_000393.5 | ENSP00000364000.3 | ||
COL5A2 | ENST00000618828.1 | c.3002C>G | p.Thr1001Ser | missense_variant | Exon 46 of 47 | 5 | ENSP00000482184.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152046Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251284Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135818
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461676Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727146
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152046Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74270
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, classic type, 1 Uncertain:1
This sequence change replaces threonine with serine at codon 1388 of the COL5A2 protein (p.Thr1388Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. This variant is present in population databases (rs771415085, ExAC 0.01%). This variant has not been reported in the literature in individuals with COL5A2-related conditions. 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 not expected to disrupt COL5A2 protein function. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at