Variant chr17-44851802-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate

The NM_004247.4(EFTUD2):c.2731C>T(p.Pro911Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

EFTUD2
NM_004247.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.27

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 Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), EFTUD2. . Gene score misZ 4.0264 (greater than the threshold 3.09). Trascript score misZ 5.3556 (greater than threshold 3.09). GenCC has associacion of gene with mandibulofacial dysostosis-microcephaly syndrome.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.865

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EFTUD2	NM_004247.4 linkuse as main transcript	c.2731C>T	p.Pro911Ser	missense_variant	27/28	ENST00000426333.7	NP_004238.3
EFTUD2	NM_001258353.2 linkuse as main transcript	c.2731C>T	p.Pro911Ser	missense_variant	27/28		NP_001245282.1
EFTUD2	NM_001258354.2 linkuse as main transcript	c.2701C>T	p.Pro901Ser	missense_variant	27/28		NP_001245283.1
EFTUD2	NM_001142605.2 linkuse as main transcript	c.2626C>T	p.Pro876Ser	missense_variant	26/27		NP_001136077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFTUD2	ENST00000426333.7 linkuse as main transcript	c.2731C>T	p.Pro911Ser	missense_variant	27/28	1	NM_004247.4	ENSP00000392094	P1	Q15029-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.54

D;.;D;.;.

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

1.0

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

.;D;D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.87

D;D;D;D;D

MetaSVM

Uncertain

-0.11

MutationAssessor

Pathogenic

4.2

H;.;H;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-7.5

D;.;.;.;D

REVEL

Uncertain

0.56

Sift

Pathogenic

0.0

D;.;.;.;D

Sift4G

Uncertain

0.026

D;D;D;D;D

Polyphen

1.0

D;.;D;.;.

Vest4

0.83

MutPred

0.65

Loss of methylation at K914 (P = 0.0592);.;Loss of methylation at K914 (P = 0.0592);.;.;

MVP

0.69

MPC

2.5

ClinPred

1.0

GERP RS

5.2

Varity_R

0.91

gMVP

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over