rs200405052
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000393.5(COL5A2):c.1006-8G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,610,796 control chromosomes in the GnomAD database, with no homozygous occurrence. 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
NM_000393.5 splice_region, splice_polypyrimidine_tract, 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 | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.1006-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000374866.9 | |||
COL5A2 | XM_011510573.4 | c.868-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
COL5A2 | XM_047443251.1 | c.868-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
COL5A2 | XM_047443252.1 | c.868-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.1006-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000393.5 | P1 | |||
COL5A2 | ENST00000618828.1 | c.358+503G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152042Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251348Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135838
GnomAD4 exome AF: 0.0000213 AC: 31AN: 1458754Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 725892
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152042Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74272
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 26, 2018 | 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | COL5A2: PM2, BP4 - |
Ehlers-Danlos syndrome, classic type Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Aug 01, 2017 | COL5A2 NM_000393.3 (c.1006-8G>A): This variant has not been reported in the literature. This variant is present in 2/246126 individuals of different ethnicities in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs200405052). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. In summary, data on this variant is insufficient for disease classification. This variant is an intronic variant with no predicted change in the amino acid sequence but may have an unknown effect on splicing. Further studies are needed to understand its impact. Therefore, the clinical significance of this variant is uncertain. - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 03, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at