3-186783615-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP5

The NM_001967.4(EIF4A2):​c.5C>G​(p.Ser2Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2F) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

EIF4A2
NM_001967.4 missense

Scores

1
9
9

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.07
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP5
Variant 3-186783615-C-G is Pathogenic according to our data. Variant chr3-186783615-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1712514.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-186783615-C-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EIF4A2NM_001967.4 linkc.5C>G p.Ser2Cys missense_variant Exon 1 of 11 ENST00000323963.10 NP_001958.2 Q14240-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EIF4A2ENST00000323963.10 linkc.5C>G p.Ser2Cys missense_variant Exon 1 of 11 1 NM_001967.4 ENSP00000326381.5 Q14240-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152138
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251492
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135922
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461880
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152138
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Neurodevelopmental disorder Pathogenic:1
-
Gene Discovery Core-Manton Center, Boston Children's Hospital
Significance: Likely pathogenic
Review Status: no assertion criteria provided
Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Benign
-0.090
CADD
Pathogenic
26
DANN
Uncertain
0.98
DEOGEN2
Benign
0.022
T;T;T;.
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.88
D;D;D;D
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.58
D;D;D;D
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
1.8
.;.;L;L
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-1.3
N;N;N;N
REVEL
Benign
0.19
Sift
Uncertain
0.0020
D;D;D;D
Sift4G
Uncertain
0.022
D;D;D;D
Polyphen
0.88, 0.93
.;.;P;P
Vest4
0.72
MutPred
0.21
Loss of glycosylation at S2 (P = 0.0069);Loss of glycosylation at S2 (P = 0.0069);Loss of glycosylation at S2 (P = 0.0069);Loss of glycosylation at S2 (P = 0.0069);
MVP
0.43
MPC
0.021
ClinPred
0.94
D
GERP RS
4.5
RBP_binding_hub_radar
1.0
RBP_regulation_power_radar
2.7
Varity_R
0.25
gMVP
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs764605841; hg19: chr3-186501404; COSMIC: COSV60624675; COSMIC: COSV60624675; API