17-44883641-C-T

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.426+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,610,642 control chromosomes in the GnomAD database, including 289,269 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 0.61 ( 29385 hom., cov: 32)

Exomes 𝑓: 0.59 ( 259884 hom. )

Consequence

EFTUD2
NM_004247.4 splice_region, intron

Scores

Splicing: ADA: 0.00008388

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.555

Publications

25 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=-0.67).

BP6

Variant 17-44883641-C-T is Benign according to our data. Variant chr17-44883641-C-T is described in ClinVar as Benign. ClinVar VariationId is 128972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFTUD2	NM_004247.4 link	c.426+8G>A		splice_region_variant, intron_variant	Intron 5 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.426+8G>A		splice_region_variant, intron_variant	Intron 5 of 27	1	NM_004247.4	ENSP00000392094.1

Frequencies

GnomAD3 genomes

AF:

0.614

AC:

93373

AN:

151964

Hom.:

29358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.732

Gnomad AMI

AF:

0.640

Gnomad AMR

AF:

0.471

Gnomad ASJ

AF:

0.627

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.496

Gnomad FIN

AF:

0.557

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.602

Gnomad OTH

AF:

0.596

GnomAD2 exomes

AF:

0.561

AC:

141071

AN:

251344

AF XY:

0.561

show subpopulations

Gnomad AFR exome

AF:

0.730

Gnomad AMR exome

AF:

0.409

Gnomad ASJ exome

AF:

0.615

Gnomad EAS exome

AF:

0.496

Gnomad FIN exome

AF:

0.560

Gnomad NFE exome

AF:

0.602

Gnomad OTH exome

AF:

0.570

GnomAD4 exome

AF:

0.594

AC:

866578

AN:

1458558

Hom.:

259884

Cov.:

AF XY:

0.592

AC XY:

429398

AN XY:

725742

show subpopulations

African (AFR)

AF:

0.732

AC:

24452

AN:

33408

American (AMR)

AF:

0.419

AC:

18752

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.617

AC:

16113

AN:

26104

East Asian (EAS)

AF:

0.478

AC:

18987

AN:

39690

South Asian (SAS)

AF:

0.515

AC:

44376

AN:

86176

European-Finnish (FIN)

AF:

0.557

AC:

29759

AN:

53416

Middle Eastern (MID)

AF:

0.610

AC:

3513

AN:

5762

European-Non Finnish (NFE)

AF:

0.609

AC:

675203

AN:

1109022

Other (OTH)

AF:

0.588

AC:

35423

AN:

60266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

15870

31740

47611

63481

79351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18216

36432

54648

72864

91080

<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:

0.614

AC:

93441

AN:

152084

Hom.:

29385

Cov.:

AF XY:

0.604

AC XY:

44906

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.732

AC:

30365

AN:

41478

American (AMR)

AF:

0.472

AC:

7202

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.627

AC:

2175

AN:

3470

East Asian (EAS)

AF:

0.488

AC:

2517

AN:

5156

South Asian (SAS)

AF:

0.495

AC:

2392

AN:

4828

European-Finnish (FIN)

AF:

0.557

AC:

5892

AN:

10580

Middle Eastern (MID)

AF:

0.602

AC:

177

AN:

294

European-Non Finnish (NFE)

AF:

0.602

AC:

40893

AN:

67984

Other (OTH)

AF:

0.590

AC:

1247

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1859

3719

5578

7438

9297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

766

1532

2298

3064

3830

<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:

0.601

Hom.:

53115

Bravo

AF:

0.615

Asia WGS

AF:

0.474

AC:

1649

AN:

3478

EpiCase

AF:

0.595

EpiControl

AF:

0.591

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

- -

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

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

-0.67

CADD

Benign

4.8

(source)

DANN

Benign

0.74

PhyloP100

-0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000084

dbscSNV1_RF

Benign

0.012

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