dbSNP rs2289674: EFTUD2:p.Thr254Thr (chr17-44876041-A-G) – ACMG Classification: Benign (-20 pts)

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

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]

EFTUD2 links:

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
EFTUD2	NM_004247.4 link	c.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
EFTUD2	ENST00000426333.7 link	c.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.:

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.:

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.:

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

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

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. -

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

- -

Jul 03, 2018

GeneDx

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

- -

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over