2-189045901-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PP2PP3_ModerateBP6BS2
The NM_000393.5(COL5A2):c.3208C>T(p.Arg1070Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000886 in 1,613,380 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1070H) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.3208C>T | p.Arg1070Cys | missense_variant | 46/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.3070C>T | p.Arg1024Cys | missense_variant | 49/57 | ||
COL5A2 | XM_047443251.1 | c.3070C>T | p.Arg1024Cys | missense_variant | 51/59 | ||
COL5A2 | XM_047443252.1 | c.3070C>T | p.Arg1024Cys | missense_variant | 50/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.3208C>T | p.Arg1070Cys | missense_variant | 46/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000618828.1 | c.2047C>T | p.Arg683Cys | missense_variant | 39/47 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152086Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251260Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135840
GnomAD4 exome AF: 0.0000931 AC: 136AN: 1461294Hom.: 0 Cov.: 30 AF XY: 0.0000880 AC XY: 64AN XY: 726986
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152086Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74286
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 30, 2018 | The R1070C variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R1070C variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R1070C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense mutations in nearby residues have not been reported in HGMD, indicating this region of the protein may tolerate change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 05, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at