chr7-741476-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017802.4(DNAAF5):c.1024+11G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,226,746 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 13 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 6 hom. )

Consequence

DNAAF5
NM_017802.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0220

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 7-741476-G-T is Benign according to our data. Variant chr7-741476-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-741476-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-741476-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-741476-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-741476-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-741476-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-741476-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-741476-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-741476-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-741476-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-741476-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-741476-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260919.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 = 0.00696 (970/139326) while in subpopulation AFR AF = 0.024 (931/38816). AF 95% confidence interval is 0.0227. There are 13 homozygotes in GnomAd4. There are 478 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DNAAF5	NM_017802.4 link	c.1024+11G>T	intron_variant	Intron 4 of 12	ENST00000297440.11	NP_060272.3	Q86Y56-1B3KPE2
DNAAF5	NR_075098.2 link	n.984+11G>T	intron_variant	Intron 4 of 12
DNAAF5	XM_024446813.2 link	c.1024+11G>T	intron_variant	Intron 4 of 11		XP_024302581.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAAF5	ENST00000297440.11 link	c.1024+11G>T	intron_variant	Intron 4 of 12	1	NM_017802.4	ENSP00000297440.6	Q86Y56-1
DNAAF5	ENST00000440747.5 link	c.427+11G>T	intron_variant	Intron 4 of 12	2		ENSP00000403165.1	H0Y650
DNAAF5	ENST00000437419.5 link	c.340+11G>T	intron_variant	Intron 3 of 4	5		ENSP00000410788.1	H7C3B1
DNAAF5	ENST00000438961.1 link	n.493+11G>T	intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.00696

AC:

969

AN:

139236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0240

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00187

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.0000624

Gnomad OTH

AF:

0.00413

GnomAD2 exomes

AF:

0.00149

AC:

262

AN:

175406

AF XY:

0.00110

show subpopulations

Gnomad AFR exome

AF:

0.0217

Gnomad AMR exome

AF:

0.000865

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000139

Gnomad OTH exome

AF:

0.000426

GnomAD4 exome

AF:

0.000792

AC:

861

AN:

1087420

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

376

AN XY:

537844

show subpopulations

African (AFR)

AF:

0.0289

AC:

716

AN:

24774

American (AMR)

AF:

0.00124

AC:

AN:

29784

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16112

East Asian (EAS)

AF:

0.00

AC:

AN:

17040

South Asian (SAS)

AF:

0.0000264

AC:

AN:

75646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32152

Middle Eastern (MID)

AF:

0.000909

AC:

AN:

3302

European-Non Finnish (NFE)

AF:

0.0000495

AC:

AN:

848250

Other (OTH)

AF:

0.00151

AC:

AN:

40360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

122

163

204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00696

AC:

970

AN:

139326

Hom.:

Cov.:

AF XY:

0.00709

AC XY:

478

AN XY:

67396

show subpopulations

African (AFR)

AF:

0.0240

AC:

931

AN:

38816

American (AMR)

AF:

0.00187

AC:

AN:

13914

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3292

East Asian (EAS)

AF:

0.00

AC:

AN:

3914

South Asian (SAS)

AF:

0.00

AC:

AN:

3812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8410

Middle Eastern (MID)

AF:

0.00350

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000624

AC:

AN:

64064

Other (OTH)

AF:

0.00408

AC:

AN:

1960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

134

179

224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.000504

Hom.:

Bravo

AF:

0.00701

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:1

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Sep 08, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.51

(source)

DANN

Benign

0.44

PhyloP100

0.022

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over