17-44851275-C-G

Position:

• chr17-44851275-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM4 PP5_Moderate

The NM_004247.4(EFTUD2):​c.2918G>C​(p.Ter973Serext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EFTUD2 NM_004247.4 stop_lost
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.62

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_004247.4 Downstream stopcodon found after 31 codons.
• PP5: Variant 17-44851275-C-G is Pathogenic according to our data. Variant chr17-44851275-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2053177.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFTUD2	NM_004247.4	c.2918G>C	p.Ter973Serext*?	stop_lost	28/28	ENST00000426333.7	NP_004238.3
EFTUD2	NM_001258353.2	c.2918G>C	p.Ter973Serext*?	stop_lost	28/28		NP_001245282.1
EFTUD2	NM_001258354.2	c.2888G>C	p.Ter963Serext*?	stop_lost	28/28		NP_001245283.1
EFTUD2	NM_001142605.2	c.2813G>C	p.Ter938Serext*?	stop_lost	27/27		NP_001136077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFTUD2	ENST00000426333.7	c.2918G>C	p.Ter973Serext*?	stop_lost	28/28	1	NM_004247.4	ENSP00000392094.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 22, 2021

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This protein extension has been observed in individual(s) with clinical features of mandibulofacial dysostosis with microcephaly (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change disrupts the translational stop signal of the EFTUD2 mRNA. It is expected to extend the length of the EFTUD2 protein by 88 additional amino acid residues. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.85
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Uncertain	0.93	D
Vest4		0.14
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-42928643;