rs757313579

Variant names:

• chr14-49628007-C-T
• rs757313579
• NM_018139.3:c.2007+5G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018139.3(DNAAF2):​c.2007+5G>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 0.000022 in 1,410,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: DNAAF2 NM_018139.3 splice_region, intron
• Scores: Splicing: ADA: 0.9887
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.833
• Publications: 0 publications found

Genes affected

DNAAF2 (HGNC:20188): (dynein axonemal assembly factor 2) This gene encodes a highly conserved protein involved in the preassembly of dynein arm complexes which power cilia. These complexes are found in some cilia and are assembled in the cytoplasm prior to transport for cilia formation. Mutations in this gene have been associated with primary ciliary dyskinesia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

DNAAF2 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 10

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018139.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF2	NM_018139.3	MANE Select	c.2007+5G>A		splice_region intron	N/A	NP_060609.2
	DNAAF2	NM_001083908.2		c.1864-1959G>A		intron	N/A	NP_001077377.1
	DNAAF2	NM_001378453.1		c.-204-1959G>A		intron	N/A	NP_001365382.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF2	ENST00000298292.13	TSL:1 MANE Select	c.2007+5G>A		splice_region intron	N/A	ENSP00000298292.8
	DNAAF2	ENST00000406043.3	TSL:1	c.1864-1959G>A		intron	N/A	ENSP00000384862.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000447 AC: 8 AN: 179168 AF XY: 0.0000635

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000220 AC: 31 AN: 1410038 Hom.: 0 Cov.: 30 AF XY: 0.0000273 AC XY: 19 AN XY: 696506

African (AFR) AF: 0.00 AC: 0 AN: 32110

American (AMR) AF: 0.00 AC: 0 AN: 36412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25330

East Asian (EAS) AF: 0.00 AC: 0 AN: 37838

South Asian (SAS) AF: 0.000392 AC: 31 AN: 79022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50498

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084804

Other (OTH) AF: 0.00 AC: 0 AN: 58460

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Benign	0.88
PhyloP100		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Benign	0.63
SpliceAI score (max)		0.090		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: rs757313579; hg19: chr14-50094725;