17-44851282-G-C

Variant names:

• chr17-44851282-G-C
• NM_004247.4:c.2911C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_004247.4(EFTUD2):​c.2911C>G​(p.Pro971Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EFTUD2 NM_004247.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.48

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the EFTUD2 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 21 curated pathogenic missense variants (we use a threshold of 10). The gene has 25 curated benign missense variants. Gene score misZ: 4.0264 (above the threshold of 3.09). Trascript score misZ: 5.3556 (above the threshold of 3.09). GenCC associations: The gene is linked to mandibulofacial dysostosis-microcephaly syndrome.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFTUD2	NM_004247.4	c.2911C>G	p.Pro971Ala	missense_variant	Exon 28 of 28	ENST00000426333.7	NP_004238.3
EFTUD2	NM_001258353.2	c.2911C>G	p.Pro971Ala	missense_variant	Exon 28 of 28		NP_001245282.1
EFTUD2	NM_001258354.2	c.2881C>G	p.Pro961Ala	missense_variant	Exon 28 of 28		NP_001245283.1
EFTUD2	NM_001142605.2	c.2806C>G	p.Pro936Ala	missense_variant	Exon 27 of 27		NP_001136077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFTUD2	ENST00000426333.7	c.2911C>G	p.Pro971Ala	missense_variant	Exon 28 of 28	1	NM_004247.4	ENSP00000392094.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mandibulofacial dysostosis-microcephaly syndrome Uncertain:1

Jul 30, 2021

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.20	T;.;T;.;.
Eigen	Benign	0.096
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	.;D;D;D;D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.46	T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	L;.;L;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.95	N;.;.;.;N
REVEL	Uncertain	0.31
Sift	Benign	0.25	T;.;.;.;T
Sift4G	Benign	0.21	T;T;T;T;T
Polyphen		0.0090	B;.;B;.;.
Vest4		0.65
MutPred		0.31		Loss of stability (P = 0.0366);.;Loss of stability (P = 0.0366);.;.;
MVP		0.58
MPC		1.2
ClinPred		0.90	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.094
gMVP		0.62

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.

Other links and lift over

hg19: chr17-42928650;