rs761805565
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_001849.4(COL6A2):c.116-6C>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 0.0000745 in 1,610,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 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_001849.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.116-6C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000300527.9 | |||
COL6A2 | NM_058174.3 | c.116-6C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000397763.6 | |||
LOC124905043 | XR_007067910.1 | n.59G>A | non_coding_transcript_exon_variant | 1/2 | |||
COL6A2 | NM_058175.3 | c.116-6C>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.116-6C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001849.4 | P1 | |||
COL6A2 | ENST00000397763.6 | c.116-6C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_058174.3 | ||||
COL6A2 | ENST00000409416.6 | c.116-6C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | |||||
COL6A2 | ENST00000436769.5 | c.116-6C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000607 AC: 15AN: 246968Hom.: 0 AF XY: 0.0000745 AC XY: 10AN XY: 134266
GnomAD4 exome AF: 0.0000740 AC: 108AN: 1458500Hom.: 0 Cov.: 33 AF XY: 0.0000758 AC XY: 55AN XY: 725650
GnomAD4 genome AF: 0.0000789 AC: 12AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74298
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 10, 2023 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. - |
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2023 | - - |
COL6A2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 13, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at