2-151602602-G-A
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_001164507.2(NEB):c.13353C>T(p.Ala4451=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.091 ( 1 hom., cov: 0)
Exomes 𝑓: 0.44 ( 197 hom. )
Failed GnomAD Quality Control
Consequence
NEB
NM_001164507.2 synonymous
NM_001164507.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.79
Genes affected
NEB (HGNC:7720): (nebulin) This gene encodes nebulin, a giant protein component of the cytoskeletal matrix that coexists with the thick and thin filaments within the sarcomeres of skeletal muscle. In most vertebrates, nebulin accounts for 3 to 4% of the total myofibrillar protein. The encoded protein contains approximately 30-amino acid long modules that can be classified into 7 types and other repeated modules. Protein isoform sizes vary from 600 to 800 kD due to alternative splicing that is tissue-, species-,and developmental stage-specific. Of the 183 exons in the nebulin gene, at least 43 are alternatively spliced, although exons 143 and 144 are not found in the same transcript. Of the several thousand transcript variants predicted for nebulin, the RefSeq Project has decided to create three representative RefSeq records. Mutations in this gene are associated with recessive nemaline myopathy. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 2-151602602-G-A is Benign according to our data. Variant chr2-151602602-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151602602-G-A is described in Lovd as [Likely_benign]. Variant chr2-151602602-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.79 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.13353C>T | p.Ala4451= | synonymous_variant | 87/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.13353C>T | p.Ala4451= | synonymous_variant | 87/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.13353C>T | p.Ala4451= | synonymous_variant | 87/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.13353C>T | p.Ala4451= | synonymous_variant | 87/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.11601+7207C>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 2AN: 22Hom.: 1 Cov.: 0 FAILED QC
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GnomAD3 exomes AF: 0.333 AC: 2AN: 6Hom.: 1 AF XY: 0.333 AC XY: 2AN XY: 6
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.445 AC: 418AN: 940Hom.: 197 Cov.: 0 AF XY: 0.435 AC XY: 220AN XY: 506
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0909 AC: 2AN: 22Hom.: 1 Cov.: 0 AF XY: 0.167 AC XY: 2AN XY: 12
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 02, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 19, 2014 | NEB exons 82-105 are organized in three repetitive blocks of 8 exons each and be cause these blocks are nearly identical in sequence, homologous exons (e.g., exo ns 82, 90, and 98) are co-amplified and sequenced (each amplicon consists of 6 a lleles). This variant represents a nonhomologous position within the three repet itive blocks (c.13353C, c.14811T, and c.16269T). The variable alleles at this po sition are not expected to have clinical significance because these alleles do n ot alter an amino acid residue and are not located within the splice consensus s equence. - |
Nemaline myopathy 2 Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at