2-151677700-G-A
Variant names:
Variant summary
Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_StrongBP6_Very_StrongBP7BS1BS2_Supporting
The NM_001164507.2(NEB):c.3639C>T(p.Val1213Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000313 in 1,613,854 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 3 hom. )
Consequence
NEB
NM_001164507.2 synonymous
NM_001164507.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.460
Publications
1 publications found
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]
NEB Gene-Disease associations (from GenCC):
- nemaline myopathy 2Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P, Ambry Genetics
- childhood-onset nemaline myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- intermediate nemaline myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- typical nemaline myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- lethal multiple pterygium syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- severe congenital nemaline myopathyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 2-151677700-G-A is Benign according to our data. Variant chr2-151677700-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.46 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00148 (225/152172) while in subpopulation AFR AF = 0.00518 (215/41516). AF 95% confidence interval is 0.00461. There are 1 homozygotes in GnomAd4. There are 109 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAdExome4 at 3 AD,AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.3639C>T | p.Val1213Val | synonymous_variant | Exon 34 of 182 | 5 | NM_001164508.2 | ENSP00000380505.3 | ||
NEB | ENST00000427231.7 | c.3639C>T | p.Val1213Val | synonymous_variant | Exon 34 of 182 | 5 | NM_001164507.2 | ENSP00000416578.2 | ||
NEB | ENST00000409198.5 | c.3639C>T | p.Val1213Val | synonymous_variant | Exon 34 of 150 | 5 | ENSP00000386259.1 |
Frequencies
GnomAD3 genomes AF: 0.00147 AC: 224AN: 152054Hom.: 1 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
224
AN:
152054
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.000357 AC: 89AN: 249228 AF XY: 0.000237 show subpopulations
GnomAD2 exomes
AF:
AC:
89
AN:
249228
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000192 AC: 280AN: 1461682Hom.: 3 Cov.: 31 AF XY: 0.000160 AC XY: 116AN XY: 727126 show subpopulations
GnomAD4 exome
AF:
AC:
280
AN:
1461682
Hom.:
Cov.:
31
AF XY:
AC XY:
116
AN XY:
727126
show subpopulations
African (AFR)
AF:
AC:
257
AN:
33478
American (AMR)
AF:
AC:
3
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53402
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1111846
Other (OTH)
AF:
AC:
17
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.458
Heterozygous variant carriers
0
17
34
51
68
85
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.00148 AC: 225AN: 152172Hom.: 1 Cov.: 32 AF XY: 0.00147 AC XY: 109AN XY: 74374 show subpopulations
GnomAD4 genome
AF:
AC:
225
AN:
152172
Hom.:
Cov.:
32
AF XY:
AC XY:
109
AN XY:
74374
show subpopulations
African (AFR)
AF:
AC:
215
AN:
41516
American (AMR)
AF:
AC:
5
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
AC:
0
AN:
10582
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
2
AN:
68002
Other (OTH)
AF:
AC:
3
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
10
20
31
41
51
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Dec 28, 2015
Eurofins Ntd Llc (ga)
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
-
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not provided Benign:1
Jan 15, 2019
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Nemaline myopathy 2 Benign:1
Jan 12, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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