rs771438684
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PP2BP4
The NM_000089.4(COL1A2):c.3311G>A(p.Ser1104Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S1104S) has been classified as Likely benign.
Frequency
Consequence
NM_000089.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL1A2 | NM_000089.4 | c.3311G>A | p.Ser1104Asn | missense_variant | 49/52 | ENST00000297268.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL1A2 | ENST00000297268.11 | c.3311G>A | p.Ser1104Asn | missense_variant | 49/52 | 1 | NM_000089.4 | P1 | |
COL1A2 | ENST00000464916.1 | n.359G>A | non_coding_transcript_exon_variant | 1/4 | 2 | ||||
COL1A2 | ENST00000481570.5 | n.4092G>A | non_coding_transcript_exon_variant | 6/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251318Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135820
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461870Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727230
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74316
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 | Oct 18, 2023 | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1104 of the COL1A2 protein (p.Ser1104Asn). This variant is present in population databases (rs771438684, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 526883). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL1A2 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