chr21-46112092-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001849.4(COL6A2):āc.229T>Cā(p.Phe77Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,613,036 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.
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.229T>C | p.Phe77Leu | missense_variant | 3/28 | ENST00000300527.9 | |
COL6A2 | NM_058174.3 | c.229T>C | p.Phe77Leu | missense_variant | 3/28 | ENST00000397763.6 | |
COL6A2 | NM_058175.3 | c.229T>C | p.Phe77Leu | missense_variant | 3/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.229T>C | p.Phe77Leu | missense_variant | 3/28 | 1 | NM_001849.4 | P1 | |
COL6A2 | ENST00000397763.6 | c.229T>C | p.Phe77Leu | missense_variant | 3/28 | 5 | NM_058174.3 | ||
COL6A2 | ENST00000409416.6 | c.229T>C | p.Phe77Leu | missense_variant | 2/27 | 5 | |||
COL6A2 | ENST00000436769.5 | c.229T>C | p.Phe77Leu | missense_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152128Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000404 AC: 59AN: 1460908Hom.: 0 Cov.: 33 AF XY: 0.0000330 AC XY: 24AN XY: 726744
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74312
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 30, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 04, 2018 | - - |
Bethlem myopathy 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2021 | This sequence change replaces phenylalanine with leucine at codon 77 of the COL6A2 protein (p.Phe77Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with clinical suspicion of limb-girdle muscular dystrophy (PMID: 30564623). ClinVar contains an entry for this variant (Variation ID: 289146). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at