2-151485795-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM2PP3_StrongBP6
The NM_001164507.2(NEB):c.25543G>A(p.Gly8515Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,612,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001164507.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.25543G>A | p.Gly8515Arg | missense_variant | 182/182 | ENST00000427231.7 | NP_001157979.2 | |
NEB | NM_001164508.2 | c.25543G>A | p.Gly8515Arg | missense_variant | 182/182 | ENST00000397345.8 | NP_001157980.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.25543G>A | p.Gly8515Arg | missense_variant | 182/182 | 5 | NM_001164508.2 | ENSP00000380505 | P5 | |
NEB | ENST00000427231.7 | c.25543G>A | p.Gly8515Arg | missense_variant | 182/182 | 5 | NM_001164507.2 | ENSP00000416578 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248218Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134550
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460484Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726294
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 27, 2024 | The c.19975G>A (p.G6659R) alteration is located in exon 150 (coding exon 148) of the NEB gene. This alteration results from a G to A substitution at nucleotide position 19975, causing the glycine (G) at amino acid position 6659 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Nemaline myopathy 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 24, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at