rs35226268
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004836.7(EIF2AK3):c.2014G>A(p.Glu672Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,614,120 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_004836.7 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 |
---|---|---|---|---|---|---|---|
EIF2AK3 | NM_004836.7 | c.2014G>A | p.Glu672Lys | missense_variant | 12/17 | ENST00000303236.9 | |
EIF2AK3 | NM_001313915.2 | c.1561G>A | p.Glu521Lys | missense_variant | 12/17 | ||
EIF2AK3 | XM_047446428.1 | c.1723G>A | p.Glu575Lys | missense_variant | 12/17 | ||
EIF2AK3 | XM_047446429.1 | c.1330G>A | p.Glu444Lys | missense_variant | 10/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EIF2AK3 | ENST00000303236.9 | c.2014G>A | p.Glu672Lys | missense_variant | 12/17 | 1 | NM_004836.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000986 AC: 150AN: 152164Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00203 AC: 509AN: 251252Hom.: 4 AF XY: 0.00194 AC XY: 263AN XY: 135780
GnomAD4 exome AF: 0.00104 AC: 1522AN: 1461838Hom.: 23 Cov.: 31 AF XY: 0.00102 AC XY: 741AN XY: 727220
GnomAD4 genome ? AF: 0.000978 AC: 149AN: 152282Hom.: 2 Cov.: 32 AF XY: 0.00115 AC XY: 86AN XY: 74464
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Sep 15, 2016 | - - |
Wolcott-Rallison dysplasia Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 31, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
EIF2AK3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 11, 2023 | This variant is classified as likely 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