rs140109751
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP6
The NM_000393.5(COL5A2):c.4409C>T(p.Ala1470Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,694 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. A1470T) has been classified as Likely benign.
Frequency
Consequence
NM_000393.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.4409C>T | p.Ala1470Val | missense_variant | 54/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.4271C>T | p.Ala1424Val | missense_variant | 57/57 | ||
COL5A2 | XM_047443251.1 | c.4271C>T | p.Ala1424Val | missense_variant | 59/59 | ||
COL5A2 | XM_047443252.1 | c.4271C>T | p.Ala1424Val | missense_variant | 58/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.4409C>T | p.Ala1470Val | missense_variant | 54/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000618828.1 | c.3248C>T | p.Ala1083Val | missense_variant | 47/47 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461694Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727140
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 30, 2015 | The p.A1470V variant (also known as c.4409C>T), located in coding exon 54 of the COL5A2 gene, results from a C to T substitution at nucleotide position 4409. The alanine at codon 1470 is replaced by valine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs140109751. Based on data from the NHLBI Exome Sequencing Project (ESP), the T allele has an overall frequency of approximately 0.01% (1/13006) total alleles studied, having been observed in 0.02% (1/4406) African American alleles. This amino acid position is 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 variant remains unclear. - |
Ehlers-Danlos syndrome, classic type Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at