3-186784952-C-CT

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PVS1_StrongPM2BP6

The NM_001967.4(EIF4A2):​c.209-3dupT variant causes a splice acceptor, intron change. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

EIF4A2
NM_001967.4 splice_acceptor, intron

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.58
Variant links:
Genes affected
EIF4A2 (HGNC:3284): (eukaryotic translation initiation factor 4A2) Enables ATP hydrolysis activity. Involved in negative regulation of RNA-directed 5'-3' RNA polymerase activity. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
SNORD2 (HGNC:32678): (small nucleolar RNA, C/D box 2)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.114379086 fraction of the gene. Cryptic splice site detected, with MaxEntScore 10, offset of 0 (no position change), new splice context is: tgtatcctacttttttttAGggt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 3-186784952-C-CT is Benign according to our data. Variant chr3-186784952-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 3031625.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EIF4A2NM_001967.4 linkc.209-3dupT splice_acceptor_variant, intron_variant Intron 3 of 10 ENST00000323963.10 NP_001958.2 Q14240-1
SNORD2NR_002587.1 linkn.*87_*88insT downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EIF4A2ENST00000323963.10 linkc.209-3dupT splice_acceptor_variant, intron_variant Intron 3 of 10 1 NM_001967.4 ENSP00000326381.5 Q14240-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.84e-7
AC:
1
AN:
1461810
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

EIF4A2-related disorder Benign:1
Sep 23, 2020
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1721607584; hg19: chr3-186502741; API