chr2-151636277-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001164508.2(NEB):c.9052G>A(p.Asp3018Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000754 in 1,610,202 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001164508.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.9052G>A | p.Asp3018Asn | missense_variant | Exon 64 of 182 | 5 | NM_001164508.2 | ENSP00000380505.3 | ||
NEB | ENST00000427231.7 | c.9052G>A | p.Asp3018Asn | missense_variant | Exon 64 of 182 | 5 | NM_001164507.2 | ENSP00000416578.2 | ||
NEB | ENST00000409198.5 | c.8853+3616G>A | intron_variant | Intron 62 of 149 | 5 | ENSP00000386259.1 |
Frequencies
GnomAD3 genomes AF: 0.00105 AC: 160AN: 152222Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.00255 AC: 629AN: 246288Hom.: 10 AF XY: 0.00236 AC XY: 316AN XY: 133884
GnomAD4 exome AF: 0.000724 AC: 1056AN: 1457862Hom.: 14 Cov.: 31 AF XY: 0.000702 AC XY: 509AN XY: 725338
GnomAD4 genome AF: 0.00104 AC: 158AN: 152340Hom.: 3 Cov.: 32 AF XY: 0.00126 AC XY: 94AN XY: 74500
ClinVar
Submissions by phenotype
not specified Benign:3
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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not provided Benign:3
Variant summary: The c.9052G>A (p.Asp3018Asn) in NEB gene is a missense change that alters a conserved nucleotide and 4/4 in silico tools predict damaging outcome. The variant is located within conserved nebulin repeats, although the impact of this change is yet to be confirmed by functional studies. The variant is present in the large control population datasets of ExAC and gnomAD at similar frequency (264/117446 chrs and 668/274324 chrs, respectively), predominantly East Asian sub-population [0.0310 (257/8286 chrs) in ExAC and 0.03452 (648/18770 chrs tested, including 10 homozygotes) in gnomAD]. These frequencies exceed the estimated maximal expected allele frequency of a pathogenic variant in NEB gene (0.0035). This variant has been reported in two siblings from a family with nemaline myopathy in compound heterozygous state with p.Ser8228Ser (Chen_2013); whether this genotype explained the phenotype in the family is unknown. Lastly, a reputable database/diagnostic center has classified the variant of interest as benign. Taken together, the variant was classified as Benign. -
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NEB: BP4, BS1, BS2 -
Nemaline myopathy 2 Benign:1
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Nemaline myopathy 2;C5543431:Arthrogryposis multiplex congenita 6 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at