rs778385867
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_000393.5(COL5A2):c.1352C>T(p.Ser451Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,918 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S451P) has been classified as Likely benign.
Frequency
Consequence
NM_000393.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.1352C>T | p.Ser451Phe | missense_variant | 21/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.1214C>T | p.Ser405Phe | missense_variant | 24/57 | ||
COL5A2 | XM_047443251.1 | c.1214C>T | p.Ser405Phe | missense_variant | 26/59 | ||
COL5A2 | XM_047443252.1 | c.1214C>T | p.Ser405Phe | missense_variant | 25/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.1352C>T | p.Ser451Phe | missense_variant | 21/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000618828.1 | c.359-1631C>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251130Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135722
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461772Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727194
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74312
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 21, 2023 | - - |
Ehlers-Danlos syndrome, classic type, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | May 14, 2020 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 02, 2023 | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function - |
Ehlers-Danlos syndrome, classic type, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2023 | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 451 of the COL5A2 protein (p.Ser451Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL5A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 529262). 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 with a negative predictive value of 80%. 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