rs2288210
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001164507.2(NEB):āc.18305G>Cā(p.Arg6102Thr) variant causes a missense change. The variant allele was found at a frequency of 0.667 in 1,593,254 control chromosomes in the GnomAD database, including 357,250 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R6102G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001164507.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.18305G>C | p.Arg6102Thr | missense_variant | 116/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.18305G>C | p.Arg6102Thr | missense_variant | 116/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.18305G>C | p.Arg6102Thr | missense_variant | 116/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.18305G>C | p.Arg6102Thr | missense_variant | 116/182 | 5 | NM_001164507.2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.662 AC: 100598AN: 152024Hom.: 33579 Cov.: 33
GnomAD3 exomes AF: 0.667 AC: 161643AN: 242204Hom.: 54599 AF XY: 0.657 AC XY: 86124AN XY: 131084
GnomAD4 exome AF: 0.667 AC: 961578AN: 1441112Hom.: 323622 Cov.: 36 AF XY: 0.662 AC XY: 475064AN XY: 717328
GnomAD4 genome AF: 0.662 AC: 100708AN: 152142Hom.: 33628 Cov.: 33 AF XY: 0.665 AC XY: 49454AN XY: 74382
ClinVar
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 26, 2014 | This is a RefSeq error. The reference base (c.18305G) is the minor allele. This allele (G) has been identified in 34% (2760/8198) of European American chromosom es and 38% (1400/3680) of African American chromosomes by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs2288210) and thus meets criteria to be classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 05, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 05, 2013 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Nemaline myopathy 2 Benign:4
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 27, 2017 | Variant summary: The NEB c.18305G>C (p.Arg6102Thr) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 75124/112008 control chromosomes (24879 homozygotes) at a frequency of 0.6707021, which is approximately 190 times the estimated maximal expected allele frequency of a pathogenic NEB variant (0.0035355), suggesting this variant is likely a benign polymorphism. The variant of interest has been reported in a patient affected with muscular dystrophy for which a spicing variant in CHKB likely can explain the phenoytpe. This variant has also been reported in an acral melanoma sample witout evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign. - |
Arthrogryposis multiplex congenita 6 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at