NM_017802.4:c.707A>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_017802.4(DNAAF5):c.707A>T(p.His236Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000265 in 1,614,190 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

DNAAF5
NM_017802.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.50

Publications

0 publications found

Variant links:

Genes affected

DNAAF5 (HGNC:26013): (dynein axonemal assembly factor 5) The protein encoded by this gene is essential for the preassembly or stability of axonemal dynein arms, and is found only in organisms with motile cilia and flagella. Mutations in this gene are associated with primary ciliary dyskinesia-18, a disorder characterized by abnormalities of motile cilia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]

DNAAF5 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 18
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAAF5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0109606385).

BP6

Variant 7-729774-A-T is Benign according to our data. Variant chr7-729774-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 241209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-729774-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 241209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-729774-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 241209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-729774-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 241209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-729774-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 241209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-729774-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 241209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-729774-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 241209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-729774-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 241209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-729774-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 241209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-729774-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 241209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-729774-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 241209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-729774-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 241209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00148 (225/152314) while in subpopulation AFR AF = 0.00517 (215/41574). AF 95% confidence interval is 0.00461. There are 1 homozygotes in GnomAd4. There are 119 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF5	NM_017802.4 link	c.707A>T	p.His236Leu	missense_variant	Exon 2 of 13	ENST00000297440.11	NP_060272.3	Q86Y56-1B3KPE2
DNAAF5	XM_024446813.2 link	c.707A>T	p.His236Leu	missense_variant	Exon 2 of 12		XP_024302581.1
DNAAF5	NR_075098.2 link	n.667A>T		non_coding_transcript_exon_variant	Exon 2 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAAF5	ENST00000297440.11 link	c.707A>T	p.His236Leu	missense_variant	Exon 2 of 13	1	NM_017802.4	ENSP00000297440.6	Q86Y56-1
DNAAF5	ENST00000440747.5 link	c.110A>T	p.His37Leu	missense_variant	Exon 2 of 13	2		ENSP00000403165.1	H0Y650
DNAAF5	ENST00000438961.1 link	n.176A>T		non_coding_transcript_exon_variant	Exon 2 of 5	4
DNAAF5	ENST00000437419.5 link	c.96+2459A>T		intron_variant	Intron 1 of 4	5		ENSP00000410788.1	H7C3B1

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

224

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00516

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000370

AC:

AN:

251126

AF XY:

0.000294

show subpopulations

Gnomad AFR exome

AF:

0.00567

Gnomad AMR exome

AF:

0.0000289

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:

0.000139

AC:

203

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00553

AC:

185

AN:

33480

American (AMR)

AF:

0.0000894

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112006

Other (OTH)

AF:

0.000215

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

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

AF:

0.00148

AC:

225

AN:

152314

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00517

AC:

215

AN:

41574

American (AMR)

AF:

0.000327

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.0000856

Hom.:

Bravo

AF:

0.00152

ExAC

AF:

0.000461

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:2

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 07, 2019

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

DNAAF5-related disorder

Benign:1

Dec 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.21

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.53

M_CAP

Benign

0.021

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.95

PhyloP100

5.5

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.3

REVEL

Benign

0.21

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0040

Polyphen

0.0020

Vest4

0.40

MVP

0.25

MPC

0.20

ClinPred

0.050

GERP RS

5.2

Varity_R

0.22

gMVP

0.30

Mutation Taster

=72/28

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over