chr2-151490016-T-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_001164507.2(NEB):c.25359A>C(p.Gln8453His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,613,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. Q8453Q) has been classified as Likely benign.
Frequency
Consequence
NM_001164507.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.25359A>C | p.Gln8453His | missense_variant | 181/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.25359A>C | p.Gln8453His | missense_variant | 181/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.25359A>C | p.Gln8453His | missense_variant | 181/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.25359A>C | p.Gln8453His | missense_variant | 181/182 | 5 | NM_001164507.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152134Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248888Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134986
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461318Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726976
GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74328
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:1Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
NEB-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 31, 2023 | The NEB c.25464A>C variant is predicted to result in the amino acid substitution p.Gln8488His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.033% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-152346530-T-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at