Variant rs11654183 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004247.4(EFTUD2):c.994+6C>T variant causes a splice donor 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. 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_donor_region, intron

Scores

Splicing: ADA: 0.00003383

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.330

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 128974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-44872440-G-A is described in Lovd as [Benign].

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/exons	MANE	UniProt
EFTUD2	NM_004247.4 linkuse as main transcript	c.994+6C>T		splice_donor_region_variant, intron_variant		ENST00000426333.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFTUD2	ENST00000426333.7 linkuse as main transcript	c.994+6C>T		splice_donor_region_variant, intron_variant		1	NM_004247.4	P1	Q15029-1

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

GnomAD3 exomes

AF:

0.268

AC:

67339

AN:

251090

Hom.:

9317

AF XY:

0.269

AC XY:

36500

AN XY:

135724

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 SAS exome

AF:

0.282

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

Gnomad4 AFR exome

AF:

0.234

Gnomad4 AMR exome

AF:

0.225

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.214

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.316

Gnomad4 NFE exome

AF:

0.277

Gnomad4 OTH exome

AF:

0.264

GnomAD4 genome

AF:

0.262

AC:

39856

AN:

152082

Hom.:

5285

Cov.:

AF XY:

0.262

AC XY:

19459

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.233

Gnomad4 AMR

AF:

0.227

Gnomad4 ASJ

AF:

0.242

Gnomad4 EAS

AF:

0.248

Gnomad4 SAS

AF:

0.271

Gnomad4 FIN

AF:

0.318

Gnomad4 NFE

AF:

0.281

Gnomad4 OTH

AF:

0.263

Alfa

AF:

0.270

Hom.:

3624

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:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 20, 2018	- -

Mandibulofacial dysostosis-microcephaly syndrome

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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

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