rs202044707
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_001164507.2(NEB):c.8071C>T(p.Arg2691Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000483 in 1,613,794 control chromosomes in the GnomAD database, including 1 homozygotes. 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. R2691H) has been classified as Likely benign.
Frequency
Consequence
NM_001164507.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.8071C>T | p.Arg2691Cys | missense_variant | 58/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.8071C>T | p.Arg2691Cys | missense_variant | 58/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.8071C>T | p.Arg2691Cys | missense_variant | 58/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.8071C>T | p.Arg2691Cys | missense_variant | 58/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.8071C>T | p.Arg2691Cys | missense_variant | 58/150 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152076Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.0000482 AC: 12AN: 249120Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135136
GnomAD4 exome AF: 0.0000376 AC: 55AN: 1461600Hom.: 0 Cov.: 31 AF XY: 0.0000440 AC XY: 32AN XY: 727094
GnomAD4 genome ? AF: 0.000151 AC: 23AN: 152194Hom.: 1 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74402
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:2Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 14, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at