rs2050453609

Variant names:

• chr17-44851698-A-G
• rs2050453609
• NM_004247.4:c.2823+12T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_004247.4(EFTUD2):​c.2823+12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,427,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EFTUD2 NM_004247.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.33
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-44851698-A-G is Benign according to our data. Variant chr17-44851698-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1938747.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2823+12T>C		intron	N/A	NP_004238.3
	EFTUD2	NM_001258353.2		c.2823+12T>C		intron	N/A	NP_001245282.1	Q15029-1
	EFTUD2	NM_001258354.2		c.2793+12T>C		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.2823+12T>C		intron	N/A	ENSP00000392094.1	Q15029-1
	EFTUD2	ENST00000969864.1		c.2991+12T>C		intron	N/A	ENSP00000639923.1
	EFTUD2	ENST00000880576.1		c.2847+12T>C		intron	N/A	ENSP00000550635.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1427932 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 708600

African (AFR) AF: 0.00 AC: 0 AN: 31870

American (AMR) AF: 0.00 AC: 0 AN: 36138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24656

East Asian (EAS) AF: 0.00 AC: 0 AN: 39088

South Asian (SAS) AF: 0.00 AC: 0 AN: 80048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5564

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1099190

Other (OTH) AF: 0.00 AC: 0 AN: 59016

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.9
DANN	Benign	0.52
PhyloP100		1.3

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: rs2050453609; hg19: chr17-42929066;