2-151525171-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001164507.2(NEB):c.22264C>A(p.Gln7422Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,612,538 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q7422E) has been classified as Uncertain significance.
Frequency
Consequence
NM_001164507.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.22264C>A | p.Gln7422Lys | missense_variant | 151/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.22264C>A | p.Gln7422Lys | missense_variant | 151/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.22264C>A | p.Gln7422Lys | missense_variant | 151/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.22264C>A | p.Gln7422Lys | missense_variant | 151/182 | 5 | NM_001164507.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152222Hom.: 0 Cov.: 30
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460316Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726536
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152222Hom.: 0 Cov.: 30 AF XY: 0.0000269 AC XY: 2AN XY: 74368
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 26, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 30, 2023 | This variant has not been reported in the literature in individuals affected with NEB-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 465562). This variant is present in population databases (rs369642754, gnomAD 0.0009%). This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 7457 of the NEB protein (p.Gln7457Lys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at