rs200307392
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BS2_Supporting
The NM_001164507.2(NEB):c.8801G>A(p.Arg2934His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0004 in 1,613,890 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2934C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001164507.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.8801G>A | p.Arg2934His | missense_variant | 62/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.8801G>A | p.Arg2934His | missense_variant | 62/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.8801G>A | p.Arg2934His | missense_variant | 62/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.8801G>A | p.Arg2934His | missense_variant | 62/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.8801G>A | p.Arg2934His | missense_variant | 62/150 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000414 AC: 63AN: 152098Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000759 AC: 189AN: 249162Hom.: 2 AF XY: 0.000688 AC XY: 93AN XY: 135160
GnomAD4 exome AF: 0.000395 AC: 577AN: 1461674Hom.: 6 Cov.: 31 AF XY: 0.000378 AC XY: 275AN XY: 727120
GnomAD4 genome ? AF: 0.000447 AC: 68AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26AN XY: 74410
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:1Benign:2
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 13, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | NEB: BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 01, 2020 | This variant is associated with the following publications: (PMID: 29178646) - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Sep 17, 2015 | - - |
NEB-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 12, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at