chr21-46125782-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001849.4(COL6A2):c.1970-3C>T 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 0.00000206 in 1,458,876 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 Uncertain significance (★).
Frequency
Consequence
NM_001849.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.1970-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000300527.9 | |||
COL6A2 | NM_058174.3 | c.1970-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000397763.6 | |||
COL6A2 | NM_058175.3 | c.1970-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.1970-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001849.4 | P1 | |||
COL6A2 | ENST00000397763.6 | c.1970-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_058174.3 | ||||
COL6A2 | ENST00000409416.6 | c.1970-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | |||||
COL6A2 | ENST00000413758.1 | c.641-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1458876Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 725410
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Bethlem myopathy 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 21, 2023 | This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 1494279). This variant has not been reported in the literature in individuals affected with COL6A2-related conditions. This sequence change falls in intron 25 of the COL6A2 gene. It does not directly change the encoded amino acid sequence of the COL6A2 protein. It affects a nucleotide within the consensus splice site. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at