15-80979291-C-CT
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_015154.3(MESD):c.632dupA(p.Lys212GlufsTer19) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,632 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_015154.3 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MESD | NM_015154.3 | c.632dupA | p.Lys212GlufsTer19 | frameshift_variant | Exon 3 of 3 | ENST00000261758.6 | NP_055969.1 | |
MESD | NR_126327.2 | n.660dupA | non_coding_transcript_exon_variant | Exon 3 of 5 | ||||
MESD | NR_126328.2 | n.241+10287dupA | intron_variant | Intron 1 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152066Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461566Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727122
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152066Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74264
ClinVar
Submissions by phenotype
not provided Pathogenic:1
This sequence change creates a premature translational stop signal (p.Lys212Glufs*19) in the MESDC2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 23 amino acid(s) of the MESDC2 protein. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. ClinVar contains an entry for this variant (Variation ID: 692262). This premature translational stop signal has been observed in individual(s) with osteogenesis imperfecta (PMID: 31564437). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. -
Osteogenesis imperfecta, type 20 Pathogenic:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at