2-151498288-A-ACTCT
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001164507.2(NEB):c.24178_24179insAGAG(p.Val8060GlufsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. V8060V) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001164507.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.24178_24179insAGAG | p.Val8060GlufsTer10 | frameshift_variant | 170/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.24178_24179insAGAG | p.Val8060GlufsTer10 | frameshift_variant | 170/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.24178_24179insAGAG | p.Val8060GlufsTer10 | frameshift_variant | 170/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.24178_24179insAGAG | p.Val8060GlufsTer10 | frameshift_variant | 170/182 | 5 | NM_001164507.2 | A2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 26, 2021 | For these reasons, this variant has been classified as Pathogenic. This variant is also known as c.24175_24178dup (p.V8060Efs*10). This premature translational stop signal has been observed in individual(s) with NEB-related conditions (PMID: 32528171). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val8095Glufs*10) in the NEB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NEB are known to be pathogenic (PMID: 25205138). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.