rs536749831

Positions:

• chr17-44868279-CTACTT-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3 BP6_Very_Strong BS1 BS2

The NM_004247.4(EFTUD2):​c.1058+3_1058+7del variant causes a splice donor 5th base, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00642 in 1,613,102 control chromosomes in the GnomAD database, including 37 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0065 (33 hom.)
• Consequence: EFTUD2 NM_004247.4 splice_donor_5th_base, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 7.75

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 -15 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• BP6: Variant 17-44868279-CTACTT-C is Benign according to our data. Variant chr17-44868279-CTACTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 259250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-44868279-CTACTT-C is described in Lovd as [Likely_pathogenic]. Variant chr17-44868279-CTACTT-C is described in Lovd as [Benign]. Variant chr17-44868279-CTACTT-C is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00518 (789/152234) while in subpopulation NFE AF= 0.00717 (488/68020). AF 95% confidence interval is 0.00665. There are 4 homozygotes in gnomad4. There are 381 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 789 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFTUD2	NM_004247.4	c.1058+3_1058+7del		splice_donor_5th_base_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.1058+3_1058+7del		splice_donor_5th_base_variant, intron_variant		1	NM_004247.4	ENSP00000392094	P1

Frequencies

GnomAD3 genomes AF: 0.00519 AC: 789 AN: 152118 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00531

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00717

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00542 AC: 1359 AN: 250748 Hom.: 4 AF XY: 0.00526 AC XY: 713 AN XY: 135536

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00402

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00125

Gnomad FIN exome AF: 0.0133

Gnomad NFE exome AF: 0.00720

Gnomad OTH exome AF: 0.00638

GnomAD4 exome AF: 0.00655 AC: 9562 AN: 1460868 Hom.: 33 AF XY: 0.00634 AC XY: 4610 AN XY: 726734

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.00444

Gnomad4 ASJ exome AF: 0.00272

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00122

Gnomad4 FIN exome AF: 0.0138

Gnomad4 NFE exome AF: 0.00726

Gnomad4 OTH exome AF: 0.00560

GnomAD4 genome AF: 0.00518 AC: 789 AN: 152234 Hom.: 4 Cov.: 31 AF XY: 0.00512 AC XY: 381 AN XY: 74456

Gnomad4 AFR AF: 0.00132

Gnomad4 AMR AF: 0.00530

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.00717

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00622 Hom.: 1

Bravo AF: 0.00424

EpiCase AF: 0.00696

EpiControl AF: 0.00653

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:6

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 31, 2016	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 29, 2019	This variant is associated with the following publications: (PMID: 23188108, 27895973) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	EFTUD2: BP4, BS1, BS2 -

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Mandibulofacial dysostosis-microcephaly syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Nov 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs536749831; hg19: chr17-42945647;