dbSNP rs773831457: DNAAF5:c.1024+13G>A (chr7-741478-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_017802.4(DNAAF5):c.1024+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000309 in 1,293,942 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 0.000028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

DNAAF5
NM_017802.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.497

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: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAAF5 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_017802.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 7-741478-G-A is Benign according to our data. Variant chr7-741478-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 260920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017802.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF5	NM_017802.4	MANE Select	c.1024+13G>A		intron	N/A	NP_060272.3
	DNAAF5	NR_075098.2		n.984+13G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAAF5	ENST00000297440.11	TSL:1 MANE Select	c.1024+13G>A	intron	N/A	ENSP00000297440.6	Q86Y56-1
DNAAF5	ENST00000852634.1		c.1105+13G>A	intron	N/A	ENSP00000522693.1
DNAAF5	ENST00000852633.1		c.1024+13G>A	intron	N/A	ENSP00000522692.1

Frequencies

GnomAD3 genomes

AF:

0.0000278

AC:

AN:

144128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000250

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:

0.0000458

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000342

AC:

AN:

175324

AF XY:

0.0000324

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000717

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000417

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000313

AC:

AN:

1149814

Hom.:

Cov.:

AF XY:

0.0000351

AC XY:

AN XY:

569562

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26136

American (AMR)

AF:

0.00

AC:

AN:

31288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18066

East Asian (EAS)

AF:

0.0000441

AC:

AN:

22698

South Asian (SAS)

AF:

0.0000523

AC:

AN:

76456

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3574

European-Non Finnish (NFE)

AF:

0.0000325

AC:

AN:

891822

Other (OTH)

AF:

0.0000455

AC:

AN:

43926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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:

0.0000278

AC:

AN:

144128

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

70182

show subpopulations

African (AFR)

AF:

0.0000250

AC:

AN:

40036

American (AMR)

AF:

0.00

AC:

AN:

14604

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3350

East Asian (EAS)

AF:

0.00

AC:

AN:

4286

South Asian (SAS)

AF:

0.00

AC:

AN:

4032

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9154

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000458

AC:

AN:

65452

Other (OTH)

AF:

0.00

AC:

AN:

2024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.00

Hom.:

Bravo

AF:

0.0000491

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.95

(source)

DANN

Benign

0.30

PhyloP100

-0.50

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over