rs367643805
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The ENST00000374866.9(COL5A2):c.3471+8A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,604,170 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
ENST00000374866.9 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.3471+8A>T | splice_region_variant, intron_variant | ENST00000374866.9 | NP_000384.2 | |||
COL5A2 | XM_011510573.4 | c.3333+8A>T | splice_region_variant, intron_variant | XP_011508875.1 | ||||
COL5A2 | XM_047443251.1 | c.3333+8A>T | splice_region_variant, intron_variant | XP_047299207.1 | ||||
COL5A2 | XM_047443252.1 | c.3333+8A>T | splice_region_variant, intron_variant | XP_047299208.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.3471+8A>T | splice_region_variant, intron_variant | 1 | NM_000393.5 | ENSP00000364000 | P1 | |||
COL5A2 | ENST00000618828.1 | c.2310+8A>T | splice_region_variant, intron_variant | 5 | ENSP00000482184 |
Frequencies
GnomAD3 genomes AF: 0.000572 AC: 87AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000532 AC: 132AN: 248048Hom.: 0 AF XY: 0.000627 AC XY: 84AN XY: 133940
GnomAD4 exome AF: 0.00115 AC: 1672AN: 1452006Hom.: 1 Cov.: 29 AF XY: 0.00113 AC XY: 815AN XY: 722714
GnomAD4 genome AF: 0.000572 AC: 87AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.000565 AC XY: 42AN XY: 74338
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | COL5A2: BP4, BS1 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 29, 2016 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 21, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 18, 2014 | 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
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 10, 2023 | - - |
Ehlers-Danlos syndrome type 7A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Disproportionate tall stature;C4707243:Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Blueprint Genetics | Jan 08, 2014 | - - |
Ehlers-Danlos syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Apr 01, 2020 | - - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 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