17-44883641-C-T

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.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:8
• Conservation: PhyloP100: -0.555

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 128972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-44883641-C-T is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
EFTUD2	NM_004247.4	c.426+8G>A		splice_region_variant, intron_variant		ENST00000426333.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFTUD2	ENST00000426333.7	c.426+8G>A		splice_region_variant, intron_variant		1	NM_004247.4	P1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93373 AN: 151964 Hom.: 29358 Cov.: 32

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

GnomAD3 exomes AF: 0.561 AC: 141071 AN: 251344 Hom.: 40574 AF XY: 0.561 AC XY: 76242 AN XY: 135846

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 SAS exome AF: 0.514

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.: 33 AF XY: 0.592 AC XY: 429398 AN XY: 725742

Gnomad4 AFR exome AF: 0.732

Gnomad4 AMR exome AF: 0.419

Gnomad4 ASJ exome AF: 0.617

Gnomad4 EAS exome AF: 0.478

Gnomad4 SAS exome AF: 0.515

Gnomad4 FIN exome AF: 0.557

Gnomad4 NFE exome AF: 0.609

Gnomad4 OTH exome AF: 0.588

GnomAD4 genome AF: 0.614 AC: 93441 AN: 152084 Hom.: 29385 Cov.: 32 AF XY: 0.604 AC XY: 44906 AN XY: 74360

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.590

Alfa AF: 0.601 Hom.: 39419

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:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

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. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

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	-0.67
Cadd	Benign	4.8
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs2289677; hg19: chr17-42961009; COSMIC: COSV68182194; COSMIC: COSV68182194;