rs201186702
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_000393.5(COL5A2):c.3170C>A(p.Thr1057Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,613,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. T1057A) has been classified as Uncertain significance.
Frequency
Consequence
NM_000393.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.3170C>A | p.Thr1057Asn | missense_variant | 45/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.3032C>A | p.Thr1011Asn | missense_variant | 48/57 | ||
COL5A2 | XM_047443251.1 | c.3032C>A | p.Thr1011Asn | missense_variant | 50/59 | ||
COL5A2 | XM_047443252.1 | c.3032C>A | p.Thr1011Asn | missense_variant | 49/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.3170C>A | p.Thr1057Asn | missense_variant | 45/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000618828.1 | c.2009C>A | p.Thr670Asn | missense_variant | 38/47 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152132Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251374Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135878
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461716Hom.: 0 Cov.: 30 AF XY: 0.0000316 AC XY: 23AN XY: 727178
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152250Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74428
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 29, 2021 | The p.T1057N variant (also known as c.3170C>A), located in coding exon 45 of the COL5A2 gene, results from a C to A substitution at nucleotide position 3170. The threonine at codon 1057 is replaced by asparagine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 21, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 10, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at