chr2-88557371-CAG-C
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_004836.7(EIF2AK3):c.*363_*364del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000369 in 241,418 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00034 ( 0 hom. )
Consequence
EIF2AK3
NM_004836.7 3_prime_UTR
NM_004836.7 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.721
Genes affected
EIF2AK3 (HGNC:3255): (eukaryotic translation initiation factor 2 alpha kinase 3) The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2, leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. This protein is thought to modulate mitochondrial function. It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. Mutations in this gene are associated with Wolcott-Rallison syndrome. [provided by RefSeq, Sep 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000387 (59/152302) while in subpopulation NFE AF= 0.000588 (40/68028). AF 95% confidence interval is 0.000444. There are 0 homozygotes in gnomad4. There are 21 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EIF2AK3 | NM_004836.7 | c.*363_*364del | 3_prime_UTR_variant | 17/17 | ENST00000303236.9 | ||
LOC101928371 | NR_110236.1 | n.651-17142_651-17141del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EIF2AK3 | ENST00000303236.9 | c.*363_*364del | 3_prime_UTR_variant | 17/17 | 1 | NM_004836.7 | P1 | ||
ENST00000413234.1 | n.651-17142_651-17141del | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.000375 AC: 57AN: 152184Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.000337 AC: 30AN: 89116Hom.: 0 AF XY: 0.000429 AC XY: 20AN XY: 46642
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GnomAD4 genome AF: 0.000387 AC: 59AN: 152302Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 21AN XY: 74472
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Wolcott-Rallison dysplasia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at