rs2289677

Variant names:

• chr17-44883641-C-T
• rs2289677
• NM_004247.4:c.426+8G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-44883641-C-T
• chr17-44883641-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004247.4(EFTUD2):​c.426+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,610,642 control chromosomes in the GnomAD database, including 289,269 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (29385 hom., cov: 32)
  • Exomes 𝑓: 0.59 (259884 hom.)
• Consequence: EFTUD2 NM_004247.4 splice_region, intron
• Scores: Splicing: ADA: 0.00008388
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.555
• Publications: 25 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 17-44883641-C-T is Benign according to our data. Variant chr17-44883641-C-T is described in ClinVar as Benign. ClinVar VariationId is 128972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFTUD2	NM_004247.4	MANE Select	c.426+8G>A		splice_region intron	N/A	NP_004238.3
	EFTUD2	NM_001258353.2		c.426+8G>A		splice_region intron	N/A	NP_001245282.1	Q15029-1
	EFTUD2	NM_001258354.2		c.426+8G>A		splice_region intron	N/A	NP_001245283.1	Q15029-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFTUD2	ENST00000426333.7	TSL:1 MANE Select	c.426+8G>A		splice_region intron	N/A	ENSP00000392094.1	Q15029-1
	EFTUD2	ENST00000969864.1		c.426+8G>A		splice_region intron	N/A	ENSP00000639923.1
	EFTUD2	ENST00000880576.1		c.426+8G>A		splice_region intron	N/A	ENSP00000550635.1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93373 AN: 151964 Hom.: 29358 Cov.: 32

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.596

GnomAD2 exomes AF: 0.561 AC: 141071 AN: 251344 AF XY: 0.561

Gnomad AFR exome AF: 0.730

Gnomad AMR exome AF: 0.409

Gnomad ASJ exome AF: 0.615

Gnomad EAS exome AF: 0.496

Gnomad FIN exome AF: 0.560

Gnomad NFE exome AF: 0.602

Gnomad OTH exome AF: 0.570

GnomAD4 exome AF: 0.594 AC: 866578 AN: 1458558 Hom.: 259884 Cov.: 33 AF XY: 0.592 AC XY: 429398 AN XY: 725742

African (AFR) AF: 0.732 AC: 24452 AN: 33408

American (AMR) AF: 0.419 AC: 18752 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 16113 AN: 26104

East Asian (EAS) AF: 0.478 AC: 18987 AN: 39690

South Asian (SAS) AF: 0.515 AC: 44376 AN: 86176

European-Finnish (FIN) AF: 0.557 AC: 29759 AN: 53416

Middle Eastern (MID) AF: 0.610 AC: 3513 AN: 5762

European-Non Finnish (NFE) AF: 0.609 AC: 675203 AN: 1109022

Other (OTH) AF: 0.588 AC: 35423 AN: 60266

GnomAD4 genome AF: 0.614 AC: 93441 AN: 152084 Hom.: 29385 Cov.: 32 AF XY: 0.604 AC XY: 44906 AN XY: 74360

African (AFR) AF: 0.732 AC: 30365 AN: 41478

American (AMR) AF: 0.472 AC: 7202 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2175 AN: 3470

East Asian (EAS) AF: 0.488 AC: 2517 AN: 5156

South Asian (SAS) AF: 0.495 AC: 2392 AN: 4828

European-Finnish (FIN) AF: 0.557 AC: 5892 AN: 10580

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40893 AN: 67984

Other (OTH) AF: 0.590 AC: 1247 AN: 2112

Alfa AF: 0.601 Hom.: 53115

Bravo AF: 0.615

Asia WGS AF: 0.474 AC: 1649 AN: 3478

EpiCase AF: 0.595

EpiControl AF: 0.591

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	2	Mandibulofacial dysostosis-microcephaly syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.8
DANN	Benign	0.74
PhyloP100		-0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000084
dbscSNV1_RF	Benign	0.012
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

Other links and lift over

dbSNP: rs2289677; hg19: chr17-42961009; COSMIC: COSV68182194; COSMIC: COSV68182194;