2-188999297-G-A
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 3P and 20B. PM1PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_000090.4(COL3A1):c.2035G>A(p.Ala679Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00727 in 1,576,684 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000090.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL3A1 | NM_000090.4 | c.2035G>A | p.Ala679Thr | missense_variant | 30/51 | ENST00000304636.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL3A1 | ENST00000304636.9 | c.2035G>A | p.Ala679Thr | missense_variant | 30/51 | 1 | NM_000090.4 | P1 | |
COL3A1 | ENST00000450867.2 | c.1936G>A | p.Ala646Thr | missense_variant | 29/50 | 1 |
Frequencies
GnomAD3 genomes AF: 0.00575 AC: 875AN: 152120Hom.: 3 Cov.: 33
GnomAD3 exomes AF: 0.00550 AC: 1037AN: 188674Hom.: 8 AF XY: 0.00559 AC XY: 563AN XY: 100758
GnomAD4 exome AF: 0.00743 AC: 10590AN: 1424446Hom.: 56 Cov.: 32 AF XY: 0.00725 AC XY: 5115AN XY: 705086
GnomAD4 genome AF: 0.00575 AC: 875AN: 152238Hom.: 3 Cov.: 33 AF XY: 0.00588 AC XY: 438AN XY: 74428
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:3
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 14, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Apr 27, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 17, 2019 | 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. - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 22, 2018 | This variant is associated with the following publications: (PMID: 18272325, 28655553) - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 10, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | COL3A1: BS2 - |
Ehlers-Danlos syndrome, type 4 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 | Invitae | Jan 31, 2024 | - - |
Ehlers-Danlos syndrome, type 4;C5193040:Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 10, 2022 | - - |
Familial aortopathy Benign:1
Likely benign, criteria provided, single submitter | curation | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 18, 2011 | - - |
Ehlers-Danlos syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jul 16, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at