Genetic Variant DNAAF2:p.His443Gln (chr14-49633821-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_018139.3(DNAAF2):c.1329C>G(p.His443Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000286 in 1,431,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H443H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

DNAAF2
NM_018139.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.246

Publications

1 publications found

Variant links:

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

DNAAF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.047557503).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAAF2	NM_018139.3	MANE Select	c.1329C>G	p.His443Gln	missense	Exon 1 of 3	NP_060609.2
DNAAF2	NM_001083908.2		c.1329C>G	p.His443Gln	missense	Exon 1 of 2	NP_001077377.1
DNAAF2	NM_001378453.1		c.-543C>G		5_prime_UTR	Exon 1 of 2	NP_001365382.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF2	ENST00000298292.13	TSL:1 MANE Select	c.1329C>G	p.His443Gln	missense	Exon 1 of 3	ENSP00000298292.8
	DNAAF2	ENST00000406043.3	TSL:1	c.1329C>G	p.His443Gln	missense	Exon 1 of 2	ENSP00000384862.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000987

AC:

AN:

202556

AF XY:

0.0000179

show subpopulations

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:

0.0000217

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000286

AC:

AN:

1431066

Hom.:

Cov.:

AF XY:

0.0000267

AC XY:

AN XY:

710984

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33028

American (AMR)

AF:

0.00

AC:

AN:

42284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25670

East Asian (EAS)

AF:

0.00

AC:

AN:

38882

South Asian (SAS)

AF:

0.00

AC:

AN:

84078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.0000362

AC:

AN:

1104480

Other (OTH)

AF:

0.0000168

AC:

AN:

59656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000427

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.5

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.00093

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.33

M_CAP

Benign

0.0034

MetaRNN

Benign

0.048

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.90

PhyloP100

-0.25

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.15

REVEL

Benign

0.025

Sift

Benign

0.80

Sift4G

Benign

0.63

Polyphen

0.0030

Vest4

0.029

MutPred

0.17

Gain of catalytic residue at P447 (P = 0.0011)

MVP

0.14

MPC

0.51

ClinPred

0.036

GERP RS

-2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.044

gMVP

0.16

Mutation Taster

=96/4

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over