rs759604513
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_000393.5(COL5A2):c.284T>A(p.Val95Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000929 in 1,614,018 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.284T>A | p.Val95Asp | missense_variant | Exon 2 of 54 | ENST00000374866.9 | NP_000384.2 | |
COL5A2 | XM_011510573.4 | c.146T>A | p.Val49Asp | missense_variant | Exon 5 of 57 | XP_011508875.1 | ||
COL5A2 | XM_047443251.1 | c.146T>A | p.Val49Asp | missense_variant | Exon 7 of 59 | XP_047299207.1 | ||
COL5A2 | XM_047443252.1 | c.146T>A | p.Val49Asp | missense_variant | Exon 6 of 58 | XP_047299208.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.284T>A | p.Val95Asp | missense_variant | Exon 2 of 54 | 1 | NM_000393.5 | ENSP00000364000.3 | ||
COL5A2 | ENST00000649966.1 | c.146T>A | p.Val49Asp | missense_variant | Exon 2 of 11 | ENSP00000496785.1 | ||||
COL5A2 | ENST00000618828.1 | c.-347T>A | 5_prime_UTR_variant | Exon 2 of 47 | 5 | ENSP00000482184.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251354Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135846
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461836Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6AN XY: 727222
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74340
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
The p.V95D variant (also known as c.284T>A), located in coding exon 2 of the COL5A2 gene, results from a T to A substitution at nucleotide position 284. The valine at codon 95 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. -
not provided Uncertain:1
Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22696272) -
Ehlers-Danlos syndrome, classic type, 1 Uncertain:1
This sequence change replaces valine with aspartic acid at codon 95 of the COL5A2 protein (p.Val95Asp). The valine residue is highly conserved and there is a large physicochemical difference between valine and aspartic acid. This variant is present in population databases (rs759604513, ExAC 0.007%). 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: 213135). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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