chr2-189051396-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_000393.5(COL5A2):c.2855G>A(p.Arg952His) variant causes a missense change. The variant allele was found at a frequency of 0.0000533 in 1,613,940 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R952C) has been classified as Likely benign.
Frequency
Consequence
NM_000393.5 missense
Scores
Clinical Significance
Conservation
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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.2855G>A | p.Arg952His | missense_variant | 42/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.2717G>A | p.Arg906His | missense_variant | 45/57 | ||
COL5A2 | XM_047443251.1 | c.2717G>A | p.Arg906His | missense_variant | 47/59 | ||
COL5A2 | XM_047443252.1 | c.2717G>A | p.Arg906His | missense_variant | 46/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.2855G>A | p.Arg952His | missense_variant | 42/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000618828.1 | c.1694G>A | p.Arg565His | missense_variant | 35/47 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251260Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135814
GnomAD4 exome AF: 0.0000479 AC: 70AN: 1461788Hom.: 0 Cov.: 31 AF XY: 0.0000536 AC XY: 39AN XY: 727188
GnomAD4 genome AF: 0.000105 AC: 16AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74322
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 09, 2021 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not located in the triple helical region, where the majority of pathogenic missense variants occur (Symoens et al., 2012; Stenson et al., 2014); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 529265; Landrum et al., 2016) - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | - - |
COL5A2-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 13, 2023 | The COL5A2 c.2855G>A variant is predicted to result in the amino acid substitution p.Arg952His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.024% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-189916122-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at