rs121912900
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Moderate
The NM_000089.4(COL1A2):c.2720G>A(p.Gly907Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G907S) has been classified as Pathogenic.
Frequency
Consequence
NM_000089.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL1A2 | NM_000089.4 | c.2720G>A | p.Gly907Asp | missense_variant | 42/52 | ENST00000297268.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL1A2 | ENST00000297268.11 | c.2720G>A | p.Gly907Asp | missense_variant | 42/52 | 1 | NM_000089.4 | P1 | |
COL1A2 | ENST00000469732.1 | n.503G>A | non_coding_transcript_exon_variant | 2/4 | 2 | ||||
COL1A2 | ENST00000481570.5 | n.2693G>A | non_coding_transcript_exon_variant | 1/8 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 12, 2022 | Affects a glycine residue in a Gly-X-Y motif in the triple helical region of the COL1A2 gene, where the majority of pathogenic missense variants occur; Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 2914942) - |
Osteogenesis imperfecta, perinatal lethal Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 15, 1989 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at