Variant rs189816059 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

DNAAF5 (HGNC:):

DNAAF5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
DNAAF5	NM_017802.4 linkuse as main transcript	c.1783+10C>T	intron_variant	ENST00000297440.11	NP_060272.3	Q86Y56-1B3KPE2
DNAAF5	XM_024446813.2 linkuse as main transcript	c.1783+10C>T	intron_variant		XP_024302581.1
DNAAF5	NR_075098.2 linkuse as main transcript	n.1743+10C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
DNAAF5	ENST00000297440.11 linkuse as main transcript	c.1783+10C>T	intron_variant	1	NM_017802.4	ENSP00000297440.6	Q86Y56-1
DNAAF5	ENST00000440747.5 linkuse as main transcript	c.1186+10C>T	intron_variant	2		ENSP00000403165.1	H0Y650
DNAAF5	ENST00000491496.1 linkuse as main transcript	n.68+10C>T	intron_variant	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

GnomAD3 exomes

AF:

0.00103

AC:

247

AN:

239472

Hom.:

AF XY:

0.00102

AC XY:

133

AN XY:

130562

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 SAS exome

AF:

0.0000655

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

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.000148

Gnomad4 NFE exome

AF:

0.00215

Gnomad4 OTH exome

AF:

0.00312

GnomAD4 genome

AF:

0.00137

AC:

209

AN:

152364

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00193

Gnomad4 OTH

AF:

0.00237

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

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Primary ciliary dyskinesia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.5

DANN

Benign

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over