chr17-44852391-C-G

Variant names:

• chr17-44852391-C-G
• rs117345300
• NM_004247.4:c.2715+18G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004247.4(EFTUD2):​c.2715+18G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,613,486 control chromosomes in the GnomAD database, including 1,116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (69 hom., cov: 31)
  • Exomes 𝑓: 0.035 (1047 hom.)
• Consequence: EFTUD2 NM_004247.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.772
• Publications: 1 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: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-44852391-C-G is Benign according to our data. Variant chr17-44852391-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0237 (3601/152190) while in subpopulation NFE AF = 0.0389 (2648/68002). AF 95% confidence interval is 0.0377. There are 69 homozygotes in GnomAd4. There are 1608 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3601 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFTUD2	NM_004247.4	c.2715+18G>C		intron_variant	Intron 26 of 27	ENST00000426333.7	NP_004238.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFTUD2	ENST00000426333.7	c.2715+18G>C		intron_variant	Intron 26 of 27	1	NM_004247.4	ENSP00000392094.1

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3598 AN: 152072 Hom.: 69 Cov.: 31

Gnomad AFR AF: 0.00727

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.0479

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0220

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0389

Gnomad OTH AF: 0.0196

GnomAD2 exomes AF: 0.0256 AC: 6433 AN: 250992 AF XY: 0.0271

Gnomad AFR exome AF: 0.00659

Gnomad AMR exome AF: 0.0107

Gnomad ASJ exome AF: 0.0466

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0138

Gnomad NFE exome AF: 0.0369

Gnomad OTH exome AF: 0.0250

GnomAD4 exome AF: 0.0350 AC: 51097 AN: 1461296 Hom.: 1047 Cov.: 31 AF XY: 0.0346 AC XY: 25164 AN XY: 726930

African (AFR) AF: 0.00499 AC: 167 AN: 33468

American (AMR) AF: 0.0115 AC: 512 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0454 AC: 1185 AN: 26122

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39696

South Asian (SAS) AF: 0.0285 AC: 2458 AN: 86200

European-Finnish (FIN) AF: 0.0150 AC: 803 AN: 53400

Middle Eastern (MID) AF: 0.0146 AC: 80 AN: 5498

European-Non Finnish (NFE) AF: 0.0396 AC: 44076 AN: 1111864

Other (OTH) AF: 0.0300 AC: 1813 AN: 60346

GnomAD4 genome AF: 0.0237 AC: 3601 AN: 152190 Hom.: 69 Cov.: 31 AF XY: 0.0216 AC XY: 1608 AN XY: 74404

African (AFR) AF: 0.00725 AC: 301 AN: 41524

American (AMR) AF: 0.0120 AC: 184 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0479 AC: 166 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0222 AC: 107 AN: 4810

European-Finnish (FIN) AF: 0.0140 AC: 149 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0389 AC: 2648 AN: 68002

Other (OTH) AF: 0.0194 AC: 41 AN: 2110

Alfa AF: 0.0164 Hom.: 10

Bravo AF: 0.0223

Asia WGS AF: 0.00779 AC: 28 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.2
DANN	Benign	0.31
PhyloP100		0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs117345300; hg19: chr17-42929759;