rs11654183

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.994+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,610,700 control chromosomes in the GnomAD database, including 60,129 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5285 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54844 hom. )

Consequence

EFTUD2
NM_004247.4 splice_region, intron

Scores

Splicing: ADA: 0.00003383

Clinical Significance

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

Conservation

PhyloP100: 0.330

Publications

18 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=-0.74).

BP6

Variant 17-44872440-G-A is Benign according to our data. Variant chr17-44872440-G-A is described in ClinVar as Benign. ClinVar VariationId is 128974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFTUD2	NM_004247.4 link	c.994+6C>T		splice_region_variant, intron_variant	Intron 11 of 27	ENST00000426333.7	NP_004238.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFTUD2	ENST00000426333.7 link	c.994+6C>T		splice_region_variant, intron_variant	Intron 11 of 27	1	NM_004247.4	ENSP00000392094.1

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39829

AN:

151964

Hom.:

5280

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.219

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.242

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.318

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.265

GnomAD2 exomes

AF:

0.268

AC:

67339

AN:

251090

AF XY:

0.269

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.224

Gnomad ASJ exome

AF:

0.246

Gnomad EAS exome

AF:

0.249

Gnomad FIN exome

AF:

0.322

Gnomad NFE exome

AF:

0.278

Gnomad OTH exome

AF:

0.267

GnomAD4 exome

AF:

0.273

AC:

398798

AN:

1458618

Hom.:

54844

Cov.:

AF XY:

0.274

AC XY:

198935

AN XY:

725658

show subpopulations

African (AFR)

AF:

0.234

AC:

7798

AN:

33370

American (AMR)

AF:

0.225

AC:

10047

AN:

44604

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

6233

AN:

26042

East Asian (EAS)

AF:

0.214

AC:

8446

AN:

39500

South Asian (SAS)

AF:

0.283

AC:

24338

AN:

86124

European-Finnish (FIN)

AF:

0.316

AC:

16775

AN:

53076

Middle Eastern (MID)

AF:

0.270

AC:

1549

AN:

5740

European-Non Finnish (NFE)

AF:

0.277

AC:

307736

AN:

1109972

Other (OTH)

AF:

0.264

AC:

15876

AN:

60190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

15315

30630

45944

61259

76574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10208

20416

30624

40832

51040

<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:

0.262

AC:

39856

AN:

152082

Hom.:

5285

Cov.:

AF XY:

0.262

AC XY:

19459

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.233

AC:

9657

AN:

41486

American (AMR)

AF:

0.227

AC:

3458

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

839

AN:

3470

East Asian (EAS)

AF:

0.248

AC:

1282

AN:

5170

South Asian (SAS)

AF:

0.271

AC:

1309

AN:

4822

European-Finnish (FIN)

AF:

0.318

AC:

3365

AN:

10572

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.281

AC:

19113

AN:

67982

Other (OTH)

AF:

0.263

AC:

555

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1558

3116

4674

6232

7790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.269

Hom.:

4051

Bravo

AF:

0.253

Asia WGS

AF:

0.227

AC:

787

AN:

3478

EpiCase

AF:

0.271

EpiControl

AF:

0.262

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 20, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mandibulofacial dysostosis-microcephaly syndrome

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.74

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000034

dbscSNV1_RF

Benign

0.036

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

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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