chr17-44899728-C-T

Variant names:

• chr17-44899728-C-T
• rs546976256
• ENST00000410006.6:c.-111C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000410006.6(DNAAF19):​c.-111C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000794 in 152,332 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00079 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAAF19 ENST00000410006.6 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.509
• Publications: 0 publications found

Genes affected

DNAAF19 (HGNC:32700): (coiled-coil domain containing 103) Enables protein homodimerization activity. Involved in axonemal dynein complex assembly; cilium movement; and determination of left/right symmetry. Predicted to be located in axoneme. Predicted to be part of outer dynein arm. Implicated in primary ciliary dyskinesia 17. [provided by Alliance of Genome Resources, Apr 2022]

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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000410006.6. 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
	DNAAF19	NM_213607.3	MANE Select	c.-141C>T		upstream_gene	N/A	NP_998772.1	Q8IW40-1
	DNAAF19	NM_001258395.2		c.-111C>T		upstream_gene	N/A	NP_001245324.1	Q8IW40-1
	DNAAF19	NM_001258396.2		c.-125C>T		upstream_gene	N/A	NP_001245325.1	Q8IW40-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF19	ENST00000410006.6	TSL:2	c.-111C>T		5_prime_UTR	Exon 1 of 4	ENSP00000387252.1	Q8IW40-1
	DNAAF19	ENST00000357776.6	TSL:2	c.-125C>T		5_prime_UTR	Exon 1 of 4	ENSP00000350420.2	F8W6J8
	DNAAF19	ENST00000886262.1		c.-111C>T		5_prime_UTR	Exon 1 of 4	ENSP00000556321.1

Frequencies

GnomAD3 genomes AF: 0.000802 AC: 122 AN: 152214 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00115

Gnomad OTH AF: 0.000478

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 72 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 54

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 6

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.000794 AC: 121 AN: 152332 Hom.: 0 Cov.: 31 AF XY: 0.000792 AC XY: 59 AN XY: 74492

African (AFR) AF: 0.000385 AC: 16 AN: 41590

American (AMR) AF: 0.000196 AC: 3 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00352 AC: 17 AN: 4824

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00115 AC: 78 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000693 Hom.: 0

Bravo AF: 0.000729

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Primary ciliary dyskinesia 17 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		0.51
PromoterAI		0.10	Neutral
Mutation Taster		=300/0	polymorphism

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: rs546976256; hg19: chr17-42977096;