rs778295967
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PP2PP3_Moderate
The NM_000089.4(COL1A2):c.2023C>T(p.Arg675Cys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000112 in 1,612,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R675H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000089.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL1A2 | NM_000089.4 | c.2023C>T | p.Arg675Cys | missense_variant, splice_region_variant | 33/52 | ENST00000297268.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL1A2 | ENST00000297268.11 | c.2023C>T | p.Arg675Cys | missense_variant, splice_region_variant | 33/52 | 1 | NM_000089.4 | P1 | |
COL1A2 | ENST00000461525.5 | n.112C>T | splice_region_variant, non_coding_transcript_exon_variant | 2/7 | 1 | ||||
COL1A2 | ENST00000473573.5 | n.360C>T | splice_region_variant, non_coding_transcript_exon_variant | 5/11 | 2 | ||||
COL1A2 | ENST00000497316.5 | n.420C>T | splice_region_variant, non_coding_transcript_exon_variant | 2/9 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151830Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250872Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135560
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1460862Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 726668
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151830Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74136
ClinVar
Submissions by phenotype
Osteogenesis imperfecta type I;C0268335:Ehlers-Danlos syndrome, classic type, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 24, 2023 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 580439). This missense change has been observed in individual(s) with clinical features of osteogenesis imperfecta (Invitae). This variant is present in population databases (rs778295967, gnomAD 0.008%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 675 of the COL1A2 protein (p.Arg675Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at