2-189035029-C-T
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_000393.5(COL5A2):c.4240G>A(p.Asp1414Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00127 in 1,613,852 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1414G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000393.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.4240G>A | p.Asp1414Asn | missense_variant | 53/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.4102G>A | p.Asp1368Asn | missense_variant | 56/57 | ||
COL5A2 | XM_047443251.1 | c.4102G>A | p.Asp1368Asn | missense_variant | 58/59 | ||
COL5A2 | XM_047443252.1 | c.4102G>A | p.Asp1368Asn | missense_variant | 57/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.4240G>A | p.Asp1414Asn | missense_variant | 53/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000618828.1 | c.3079G>A | p.Asp1027Asn | missense_variant | 46/47 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00111 AC: 169AN: 152056Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00142 AC: 357AN: 251200Hom.: 5 AF XY: 0.00121 AC XY: 164AN XY: 135746
GnomAD4 exome AF: 0.00129 AC: 1885AN: 1461678Hom.: 6 Cov.: 33 AF XY: 0.00126 AC XY: 919AN XY: 727146
GnomAD4 genome AF: 0.00111 AC: 169AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.00112 AC XY: 83AN XY: 74372
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 17, 2018 | This variant is associated with the following publications: (PMID: 11940702, 28152038, 26608033, 28550590) - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | COL5A2: BP4, BS1, BS2 - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 13, 2023 | - - |
COL5A2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 23, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 27, 2017 | 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, classic type, 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 07, 2018 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Ehlers-Danlos syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 01, 2019 | - - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Connective tissue disorder 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