Genetic Variant NM_017802.4:c.1024+11G>A (chr7-741476-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_017802.4(DNAAF5):c.1024+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000563 in 1,226,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000065 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

DNAAF5
NM_017802.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 7-741476-G-A is Benign according to our data. Variant chr7-741476-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2914443.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DNAAF5	NM_017802.4 link	c.1024+11G>A	intron_variant	Intron 4 of 12	ENST00000297440.11	NP_060272.3	Q86Y56-1B3KPE2
DNAAF5	NR_075098.2 link	n.984+11G>A	intron_variant	Intron 4 of 12
DNAAF5	XM_024446813.2 link	c.1024+11G>A	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>A	intron_variant	Intron 4 of 12	1	NM_017802.4	ENSP00000297440.6	Q86Y56-1
DNAAF5	ENST00000440747.5 link	c.427+11G>A	intron_variant	Intron 4 of 12	2		ENSP00000403165.1	H0Y650
DNAAF5	ENST00000437419.5 link	c.340+11G>A	intron_variant	Intron 3 of 4	5		ENSP00000410788.1	H7C3B1
DNAAF5	ENST00000438961.1 link	n.493+11G>A	intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.0000646

AC:

AN:

139238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000516

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000109

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000627

AC:

AN:

175406

AF XY:

0.0000432

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000358

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000693

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000552

AC:

AN:

1087424

Hom.:

Cov.:

AF XY:

0.0000576

AC XY:

AN XY:

537850

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24782

American (AMR)

AF:

0.0000336

AC:

AN:

29784

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16112

East Asian (EAS)

AF:

0.000352

AC:

AN:

17040

South Asian (SAS)

AF:

0.0000397

AC:

AN:

75646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32152

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3302

European-Non Finnish (NFE)

AF:

0.0000578

AC:

AN:

848248

Other (OTH)

AF:

0.0000248

AC:

AN:

40358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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:

0.0000646

AC:

AN:

139238

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

67322

show subpopulations

African (AFR)

AF:

0.0000516

AC:

AN:

38754

American (AMR)

AF:

0.00

AC:

AN:

13884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3292

East Asian (EAS)

AF:

0.00

AC:

AN:

3920

South Asian (SAS)

AF:

0.00

AC:

AN:

3812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.000109

AC:

AN:

64062

Other (OTH)

AF:

0.00

AC:

AN:

1938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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:

0.000216

Hom.:

Bravo

AF:

0.0000567

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Oct 27, 2023

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

-0.87

CADD

Benign

1.9

(source)

DANN

Benign

0.45

PhyloP100

0.022

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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