7-763984-C-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.1783+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,600,946 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 4 hom. )

Consequence

DNAAF5
NM_017802.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.196

Publications

1 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=-0.85).

BP6

Variant 7-763984-C-T is Benign according to our data. Variant chr7-763984-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 241200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00137 (209/152364) while in subpopulation AMR AF = 0.00327 (50/15310). AF 95% confidence interval is 0.00254. There are 0 homozygotes in GnomAd4. There are 100 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 4 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DNAAF5	NM_017802.4 link	c.1783+10C>T	intron_variant	Intron 8 of 12	ENST00000297440.11	NP_060272.3	Q86Y56-1B3KPE2
DNAAF5	NR_075098.2 link	n.1743+10C>T	intron_variant	Intron 8 of 12
DNAAF5	XM_024446813.2 link	c.1783+10C>T	intron_variant	Intron 8 of 11		XP_024302581.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAAF5	ENST00000297440.11 link	c.1783+10C>T	intron_variant	Intron 8 of 12	1	NM_017802.4	ENSP00000297440.6	Q86Y56-1
DNAAF5	ENST00000440747.5 link	c.1186+10C>T	intron_variant	Intron 8 of 12	2		ENSP00000403165.1	H0Y650
DNAAF5	ENST00000491496.1 link	n.68+10C>T	intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

208

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00103

AC:

247

AN:

239472

AF XY:

0.00102

show subpopulations

Gnomad AFR exome

AF:

0.000440

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000233

Gnomad NFE exome

AF:

0.00161

Gnomad OTH exome

AF:

0.00282

GnomAD4 exome

AF:

0.00184

AC:

2660

AN:

1448582

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

1219

AN XY:

721010

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

33476

American (AMR)

AF:

0.00119

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000928

AC:

AN:

86208

European-Finnish (FIN)

AF:

0.000148

AC:

AN:

40590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00215

AC:

2394

AN:

1111768

Other (OTH)

AF:

0.00312

AC:

188

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

147

294

442

589

736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<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:

0.00137

AC:

209

AN:

152364

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.000505

AC:

AN:

41582

American (AMR)

AF:

0.00327

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00193

AC:

131

AN:

68044

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.00138

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:1

Jan 25, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.85

CADD

Benign

1.5

(source)

DANN

Benign

0.57

PhyloP100

-0.20

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