2-151497655-CTCTT-C
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001164507.2(NEB):βc.24267_24270delβ(p.Arg8090SerfsTer54) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000394 in 152,122 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. E8089E) 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 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.24267_24270del | p.Arg8090SerfsTer54 | frameshift_variant | 171/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.24267_24270del | p.Arg8090SerfsTer54 | frameshift_variant | 171/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.24267_24270del | p.Arg8090SerfsTer54 | frameshift_variant | 171/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.24267_24270del | p.Arg8090SerfsTer54 | frameshift_variant | 171/182 | 5 | NM_001164507.2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152122Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000973 AC: 2AN: 205580Hom.: 0 AF XY: 0.00000911 AC XY: 1AN XY: 109734
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000426 AC: 61AN: 1430800Hom.: 0 AF XY: 0.0000367 AC XY: 26AN XY: 708426
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74296
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Pathogenic:3
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 05, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jun 21, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 10, 2024 | This sequence change creates a premature translational stop signal (p.Arg8125Serfs*54) 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). This variant is present in population databases (rs747564597, gnomAD 0.009%). This premature translational stop signal has been observed in individual(s) with nemaline myopathy (PMID: 25205138, 26197980). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 552268). For these reasons, this variant has been classified as Pathogenic. - |
Arthrogryposis multiplex congenita 6 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 12, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at