rs11654183

Positions:

• chr17-44872440-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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

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 (HGNC:):

ACMG classification

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	Protein	UniProt
EFTUD2	NM_004247.4	c.994+6C>T		splice_region_variant, intron_variant		ENST00000426333.7	NP_004238.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFTUD2	ENST00000426333.7	c.994+6C>T		splice_region_variant, intron_variant		1	NM_004247.4	ENSP00000392094.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39829 AN: 151964 Hom.: 5280 Cov.: 32

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

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.: 33 AF XY: 0.274 AC XY: 198935 AN XY: 725658

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.: 32 AF XY: 0.262 AC XY: 19459 AN XY: 74324

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:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

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

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 20, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Mandibulofacial dysostosis-microcephaly syndrome Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
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

Other links and lift over

dbSNP: rs11654183; hg19: chr17-42949808; COSMIC: COSV68184383; COSMIC: COSV68184383;