rs878854174
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_001103.4(ACTN2):c.2631_2632delTG(p.Ala878ThrfsTer61) 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 Uncertain significance (★).
Frequency
Consequence
NM_001103.4 frameshift
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACTN2 | NM_001103.4 | c.2631_2632delTG | p.Ala878ThrfsTer61 | frameshift_variant | Exon 21 of 21 | ENST00000366578.6 | NP_001094.1 | |
ACTN2 | NM_001278343.2 | c.2631_2632delTG | p.Ala878ThrfsTer61 | frameshift_variant | Exon 21 of 21 | NP_001265272.1 | ||
ACTN2 | NR_184402.1 | n.3003_3004delTG | non_coding_transcript_exon_variant | Exon 23 of 23 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Primary familial hypertrophic cardiomyopathy;C2677338:Dilated cardiomyopathy 1AA Uncertain:1
This sequence change deletes 2 nucleotides from exon 21 of the ACTN2 mRNA (c.2631_2632delTG), causing a frameshift at codon 878. This creates a premature translational stop signal in the last exon of the ACTN2 mRNA (p.Ala878Thrfs*61). While this is not anticipated to result in nonsense mediated decay, it is expected to result in a truncated ACTN2 protein. While this particular variant has not been reported in the literature, truncating variants in the last exon of genes are not necessarily deleterious (PMID: 24274751), and the clinical significance of this variant is uncertain at this time. In summary, this is a novel truncating variant with uncertain impact on protein function. 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