rs2289674

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

32 publications found

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 Gene-Disease associations (from GenCC):

mandibulofacial dysostosis-microcephaly syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

EFTUD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 128973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

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

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

GnomAD2 exomes

AF:

0.170

AC:

42782

AN:

251356

AF XY:

0.169

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 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

African (AFR)

AF:

0.259

AC:

8663

AN:

33478

American (AMR)

AF:

0.108

AC:

4820

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

4586

AN:

26134

East Asian (EAS)

AF:

0.149

AC:

5907

AN:

39698

South Asian (SAS)

AF:

0.115

AC:

9884

AN:

86242

European-Finnish (FIN)

AF:

0.161

AC:

8614

AN:

53412

Middle Eastern (MID)

AF:

0.0941

AC:

538

AN:

5716

European-Non Finnish (NFE)

AF:

0.214

AC:

238400

AN:

1111954

Other (OTH)

AF:

0.185

AC:

11193

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

13347

26694

40041

53388

66735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8296

16592

24888

33184

41480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.201

AC:

30580

AN:

152100

Hom.:

3367

Cov.:

AF XY:

0.195

AC XY:

14515

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.263

AC:

10905

AN:

41462

American (AMR)

AF:

0.116

AC:

1772

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

653

AN:

3468

East Asian (EAS)

AF:

0.144

AC:

748

AN:

5186

South Asian (SAS)

AF:

0.106

AC:

512

AN:

4818

European-Finnish (FIN)

AF:

0.154

AC:

1635

AN:

10588

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.202

AC:

13733

AN:

67974

Other (OTH)

AF:

0.156

AC:

329

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1225

2449

3674

4898

6123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.201

Hom.:

3016

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

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

- -

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. -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Jul 03, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

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

(source)

DANN

Benign

0.61

PhyloP100

-0.35

Mutation Taster

=91/9

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over