rs2289674

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004247.4(EFTUD2):​c.762T>C​(p.Thr254Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,613,850 control chromosomes in the GnomAD database, including 33,798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3367 hom., cov: 31)
Exomes 𝑓: 0.20 ( 30431 hom. )

Consequence

EFTUD2
NM_004247.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.354
Variant links:
Genes affected
EFTUD2 (HGNC:30858): (elongation factor Tu GTP binding domain containing 2) This gene encodes a GTPase which is a component of the spliceosome complex which processes precursor mRNAs to produce mature mRNAs. Mutations in this gene are associated with mandibulofacial dysostosis with microcephaly. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 17-44876041-A-G is Benign according to our data. Variant chr17-44876041-A-G is described in ClinVar as [Benign]. Clinvar id is 128973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-44876041-A-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EFTUD2NM_004247.4 linkc.762T>C p.Thr254Thr synonymous_variant Exon 10 of 28 ENST00000426333.7 NP_004238.3 Q15029-1B3KX19

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EFTUD2ENST00000426333.7 linkc.762T>C p.Thr254Thr synonymous_variant Exon 10 of 28 1 NM_004247.4 ENSP00000392094.1 Q15029-1

Frequencies

GnomAD3 genomes
AF:
0.201
AC:
30547
AN:
151982
Hom.:
3356
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.263
Gnomad AMI
AF:
0.304
Gnomad AMR
AF:
0.115
Gnomad ASJ
AF:
0.188
Gnomad EAS
AF:
0.144
Gnomad SAS
AF:
0.106
Gnomad FIN
AF:
0.154
Gnomad MID
AF:
0.0601
Gnomad NFE
AF:
0.202
Gnomad OTH
AF:
0.158
GnomAD3 exomes
AF:
0.170
AC:
42782
AN:
251356
Hom.:
3932
AF XY:
0.169
AC XY:
22918
AN XY:
135836
show subpopulations
Gnomad AFR exome
AF:
0.259
Gnomad AMR exome
AF:
0.104
Gnomad ASJ exome
AF:
0.176
Gnomad EAS exome
AF:
0.145
Gnomad SAS exome
AF:
0.112
Gnomad FIN exome
AF:
0.158
Gnomad NFE exome
AF:
0.200
Gnomad OTH exome
AF:
0.164
GnomAD4 exome
AF:
0.200
AC:
292605
AN:
1461750
Hom.:
30431
Cov.:
33
AF XY:
0.197
AC XY:
142917
AN XY:
727172
show subpopulations
Gnomad4 AFR exome
AF:
0.259
Gnomad4 AMR exome
AF:
0.108
Gnomad4 ASJ exome
AF:
0.175
Gnomad4 EAS exome
AF:
0.149
Gnomad4 SAS exome
AF:
0.115
Gnomad4 FIN exome
AF:
0.161
Gnomad4 NFE exome
AF:
0.214
Gnomad4 OTH exome
AF:
0.185
GnomAD4 genome
AF:
0.201
AC:
30580
AN:
152100
Hom.:
3367
Cov.:
31
AF XY:
0.195
AC XY:
14515
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.263
Gnomad4 AMR
AF:
0.116
Gnomad4 ASJ
AF:
0.188
Gnomad4 EAS
AF:
0.144
Gnomad4 SAS
AF:
0.106
Gnomad4 FIN
AF:
0.154
Gnomad4 NFE
AF:
0.202
Gnomad4 OTH
AF:
0.156
Alfa
AF:
0.201
Hom.:
2834
Bravo
AF:
0.204
Asia WGS
AF:
0.131
AC:
459
AN:
3478
EpiCase
AF:
0.195
EpiControl
AF:
0.189

ClinVar

Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:4
-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Genetic Services Laboratory, University of Chicago
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

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. -

-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not provided Benign:3
Feb 04, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jul 03, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Mandibulofacial dysostosis-microcephaly syndrome Benign:1
-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
5.2
DANN
Benign
0.61

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: rs2289674; hg19: chr17-42953409; COSMIC: COSV68183230; COSMIC: COSV68183230; API