21-46125986-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001849.4(COL6A2):c.2171G>T(p.Arg724Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000558 in 1,613,102 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R724C) has been classified as Likely benign.
Frequency
Consequence
NM_001849.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.2171G>T | p.Arg724Leu | missense_variant | 26/28 | ENST00000300527.9 | |
COL6A2 | NM_058174.3 | c.2171G>T | p.Arg724Leu | missense_variant | 26/28 | ENST00000397763.6 | |
COL6A2 | NM_058175.3 | c.2171G>T | p.Arg724Leu | missense_variant | 26/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.2171G>T | p.Arg724Leu | missense_variant | 26/28 | 1 | NM_001849.4 | P1 | |
COL6A2 | ENST00000397763.6 | c.2171G>T | p.Arg724Leu | missense_variant | 26/28 | 5 | NM_058174.3 | ||
COL6A2 | ENST00000409416.6 | c.2171G>T | p.Arg724Leu | missense_variant | 25/27 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152168Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000558 AC: 14AN: 251106Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135852
GnomAD4 exome AF: 0.0000561 AC: 82AN: 1460816Hom.: 0 Cov.: 79 AF XY: 0.0000592 AC XY: 43AN XY: 726700
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152286Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74450
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | COL6A2: PM2, BP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 17, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 03, 2016 | - - |
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 14, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at