rs10197596
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000393.5(COL5A2):āc.3690A>Cā(p.Thr1230=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,613,802 control chromosomes in the GnomAD database, including 9,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. T1230T) has been classified as Likely benign.
Frequency
Consequence
NM_000393.5 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.3690A>C | p.Thr1230= | synonymous_variant | 51/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.3552A>C | p.Thr1184= | synonymous_variant | 54/57 | ||
COL5A2 | XM_047443251.1 | c.3552A>C | p.Thr1184= | synonymous_variant | 56/59 | ||
COL5A2 | XM_047443252.1 | c.3552A>C | p.Thr1184= | synonymous_variant | 55/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.3690A>C | p.Thr1230= | synonymous_variant | 51/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000618828.1 | c.2529A>C | p.Thr843= | synonymous_variant | 44/47 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0962 AC: 14627AN: 152002Hom.: 739 Cov.: 31
GnomAD3 exomes AF: 0.106 AC: 26624AN: 250522Hom.: 1594 AF XY: 0.111 AC XY: 15077AN XY: 135500
GnomAD4 exome AF: 0.104 AC: 151413AN: 1461682Hom.: 8510 Cov.: 32 AF XY: 0.106 AC XY: 77299AN XY: 727144
GnomAD4 genome ? AF: 0.0962 AC: 14632AN: 152120Hom.: 739 Cov.: 31 AF XY: 0.0976 AC XY: 7262AN XY: 74376
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 31, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 05, 2012 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Ehlers-Danlos syndrome, classic type, 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 18, 2015 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Ehlers-Danlos syndrome type 7A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 17, 2017 | Variant summary: The c.3690A>C (p.Thr1230=) in COL5A2 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant eliminates a cryptic acceptor cite, however no functional studies supporting these predictions were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.1081 (12897/119348 chrs tested), including numerous homozygous occurrences. This frequency exceeds the estimated maximum allele frequency for a pathogenic allele in this gene (0.0000063). The variant of interest hasbeen reported as Benign by multiple reputable databases/clinical laboratories. Taking together, based on the prevalence of this variant in general population the variant was classified as Benign. - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at