Genetic Variant NM_004247.4:c.2800A>G (chr17-44851733-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004247.4(EFTUD2):c.2800A>G(p.Met934Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EFTUD2
NM_004247.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.41

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

mandibulofacial dysostosis-microcephaly syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

EFTUD2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004247.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EFTUD2	NM_004247.4	MANE Select	c.2800A>G	p.Met934Val	missense	Exon 27 of 28	NP_004238.3
EFTUD2	NM_001258353.2		c.2800A>G	p.Met934Val	missense	Exon 27 of 28	NP_001245282.1	Q15029-1
EFTUD2	NM_001258354.2		c.2770A>G	p.Met924Val	missense	Exon 27 of 28	NP_001245283.1	Q15029-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EFTUD2	ENST00000426333.7	TSL:1 MANE Select	c.2800A>G	p.Met934Val	missense	Exon 27 of 28	ENSP00000392094.1	Q15029-1
EFTUD2	ENST00000969864.1		c.2968A>G	p.Met990Val	missense	Exon 27 of 28	ENSP00000639923.1
EFTUD2	ENST00000880576.1		c.2824A>G	p.Met942Val	missense	Exon 27 of 28	ENSP00000550635.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1422416

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705090

African (AFR)

AF:

0.00

AC:

AN:

32092

American (AMR)

AF:

0.00

AC:

AN:

37874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24608

East Asian (EAS)

AF:

0.00

AC:

AN:

38466

South Asian (SAS)

AF:

0.00

AC:

AN:

79658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5648

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093892

Other (OTH)

AF:

0.00

AC:

AN:

58796

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

(source)

DANN

Benign

0.88

DEOGEN2

Uncertain

0.56

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.64

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

7.4

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.38

Sift

Benign

0.73

Sift4G

Benign

1.0

Polyphen

0.94

Vest4

0.81

MutPred

0.55

Loss of disorder (P = 0.0898)

MVP

0.58

MPC

1.9

ClinPred

0.76

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.52

gMVP

0.90

Mutation Taster

=9/91

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over