rs113374052

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017802.4(DNAAF5):c.921C>A(p.Ser307Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 1,588,566 control chromosomes in the GnomAD database, including 229 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 23 hom., cov: 34)

Exomes 𝑓: 0.015 ( 206 hom. )

Consequence

DNAAF5
NM_017802.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0540

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004960537).

BP6

Variant 7-741362-C-A is Benign according to our data. Variant chr7-741362-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 241211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-741362-C-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0132 (2006/152338) while in subpopulation NFE AF= 0.0199 (1352/68030). AF 95% confidence interval is 0.019. There are 23 homozygotes in gnomad4. There are 1001 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF5	NM_017802.4 link	c.921C>A	p.Ser307Arg	missense_variant	Exon 4 of 13	ENST00000297440.11	NP_060272.3	Q86Y56-1B3KPE2
DNAAF5	XM_024446813.2 link	c.921C>A	p.Ser307Arg	missense_variant	Exon 4 of 12		XP_024302581.1
DNAAF5	NR_075098.2 link	n.881C>A		non_coding_transcript_exon_variant	Exon 4 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAAF5	ENST00000297440.11 link	c.921C>A	p.Ser307Arg	missense_variant	Exon 4 of 13	1	NM_017802.4	ENSP00000297440.6	Q86Y56-1
DNAAF5	ENST00000440747.5 link	c.324C>A	p.Ser108Arg	missense_variant	Exon 4 of 13	2		ENSP00000403165.1	H0Y650
DNAAF5	ENST00000437419.5 link	c.237C>A	p.Ser79Arg	missense_variant	Exon 3 of 5	5		ENSP00000410788.1	H7C3B1
DNAAF5	ENST00000438961.1 link	n.390C>A		non_coding_transcript_exon_variant	Exon 4 of 5	4

Frequencies

GnomAD3 genomes

AF:

0.0132

AC:

2006

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00929

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0335

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0199

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0118

AC:

2495

AN:

211058

Hom.:

AF XY:

0.0116

AC XY:

1313

AN XY:

113112

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.00441

Gnomad ASJ exome

AF:

0.00775

Gnomad EAS exome

AF:

0.0000630

Gnomad SAS exome

AF:

0.00288

Gnomad FIN exome

AF:

0.0282

Gnomad NFE exome

AF:

0.0175

Gnomad OTH exome

AF:

0.00840

GnomAD4 exome

AF:

0.0148

AC:

21316

AN:

1436228

Hom.:

206

Cov.:

AF XY:

0.0146

AC XY:

10411

AN XY:

711832

show subpopulations

Gnomad4 AFR exome

AF:

0.00235

Gnomad4 AMR exome

AF:

0.00448

Gnomad4 ASJ exome

AF:

0.00771

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00347

Gnomad4 FIN exome

AF:

0.0272

Gnomad4 NFE exome

AF:

0.0168

Gnomad4 OTH exome

AF:

0.0113

GnomAD4 genome

AF:

0.0132

AC:

2006

AN:

152338

Hom.:

Cov.:

AF XY:

0.0134

AC XY:

1001

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00233

Gnomad4 AMR

AF:

0.00927

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0335

Gnomad4 NFE

AF:

0.0199

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0169

Hom.:

Bravo

AF:

0.0106

TwinsUK

AF:

0.0148

AC:

ALSPAC

AF:

0.0174

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.0159

AC:

137

ExAC

AF:

0.0107

AC:

1286

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 19, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:2

Jun 16, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 18

Benign:1

Oct 23, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.073

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0050

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.0

REVEL

Benign

0.076

Sift

Benign

0.34

Sift4G

Benign

0.40

Polyphen

0.34

Vest4

0.14

MutPred

0.29

Gain of MoRF binding (P = 0.3096);

MPC

0.24

ClinPred

0.0043

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.036

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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