NM_003289.4:c.836dupA
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_003289.4(TPM2):c.836dupA(p.Asn279LysfsTer2) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_003289.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TPM2 | NM_003289.4 | c.836dupA | p.Asn279LysfsTer2 | frameshift_variant | Exon 9 of 9 | ENST00000645482.3 | NP_003280.2 | |
TPM2 | NM_001301227.2 | c.836dupA | p.Asn279LysfsTer2 | frameshift_variant | Exon 9 of 9 | NP_001288156.1 | ||
TPM2 | NM_001301226.2 | c.773-1015dupA | intron_variant | Intron 8 of 8 | NP_001288155.1 | |||
TPM2 | NM_213674.1 | c.773-1015dupA | intron_variant | Intron 8 of 8 | NP_998839.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
TPM2-related disorder Pathogenic:1
The TPM2 c.836dupA variant is predicted to result in a frameshift and premature protein termination (p.Asn279Lysfs*2). This variant occurs in the last exon of the TPM2 gene and likely does not result in nonsense-mediated decay and only shortens the protein by five amino acids. To our knowledge, this variant has not been reported in the literature or public databases, indicating it is rare (http://gnomad.broadinstitute.org). At PreventionGenetics, we have observed the c.836dupA in an additional patient with features consistent with a TPM2-related disorder (internal data). We interpret this variant as likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.