rs3922641

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017802.4(DNAAF5):c.2228G>A(p.Arg743Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 1,613,026 control chromosomes in the GnomAD database, including 306,208 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 Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31879 hom., cov: 32)

Exomes 𝑓: 0.61 ( 274329 hom. )

Consequence

DNAAF5
NM_017802.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.716

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:

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=4.737047E-6).

BP6

Variant 7-775151-G-A is Benign according to our data. Variant chr7-775151-G-A is described in ClinVar as [Benign]. Clinvar id is 260932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF5	NM_017802.4 linkuse as main transcript	c.2228G>A	p.Arg743Lys	missense_variant	11/13	ENST00000297440.11	NP_060272.3	Q86Y56-1B3KPE2
DNAAF5	XM_024446813.2 linkuse as main transcript	c.2228G>A	p.Arg743Lys	missense_variant	11/12		XP_024302581.1
DNAAF5	NR_075098.2 linkuse as main transcript	n.2188G>A		non_coding_transcript_exon_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAAF5	ENST00000297440.11 linkuse as main transcript	c.2228G>A	p.Arg743Lys	missense_variant	11/13	1	NM_017802.4	ENSP00000297440.6	Q86Y56-1
DNAAF5	ENST00000403952.3 linkuse as main transcript	c.503G>A	p.Arg168Lys	missense_variant	4/6	1		ENSP00000384884.3	E9PGY2
DNAAF5	ENST00000440747.5 linkuse as main transcript	c.1631G>A	p.Arg544Lys	missense_variant	11/13	2		ENSP00000403165.1	H0Y650

Frequencies

GnomAD3 genomes

AF:

0.644

AC:

97883

AN:

151928

Hom.:

31830

Cov.:

show subpopulations

Gnomad AFR

AF:

0.705

Gnomad AMI

AF:

0.559

Gnomad AMR

AF:

0.673

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.625

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.666

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.603

Gnomad OTH

AF:

0.650

GnomAD3 exomes

AF:

0.623

AC:

156526

AN:

251100

Hom.:

48910

AF XY:

0.622

AC XY:

84384

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.703

Gnomad AMR exome

AF:

0.619

Gnomad ASJ exome

AF:

0.582

Gnomad EAS exome

AF:

0.633

Gnomad SAS exome

AF:

0.647

Gnomad FIN exome

AF:

0.662

Gnomad NFE exome

AF:

0.602

Gnomad OTH exome

AF:

0.615

GnomAD4 exome

AF:

0.612

AC:

894039

AN:

1460980

Hom.:

274329

Cov.:

AF XY:

0.612

AC XY:

444980

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.716

Gnomad4 AMR exome

AF:

0.627

Gnomad4 ASJ exome

AF:

0.579

Gnomad4 EAS exome

AF:

0.605

Gnomad4 SAS exome

AF:

0.644

Gnomad4 FIN exome

AF:

0.662

Gnomad4 NFE exome

AF:

0.604

Gnomad4 OTH exome

AF:

0.617

GnomAD4 genome

AF:

0.644

AC:

97980

AN:

152046

Hom.:

31879

Cov.:

AF XY:

0.647

AC XY:

48100

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.705

Gnomad4 AMR

AF:

0.673

Gnomad4 ASJ

AF:

0.561

Gnomad4 EAS

AF:

0.625

Gnomad4 SAS

AF:

0.669

Gnomad4 FIN

AF:

0.666

Gnomad4 NFE

AF:

0.603

Gnomad4 OTH

AF:

0.654

Alfa

AF:

0.611

Hom.:

46019

Bravo

AF:

0.647

TwinsUK

AF:

0.593

AC:

2199

ALSPAC

AF:

0.624

AC:

2406

ESP6500AA

AF:

0.693

AC:

3053

ESP6500EA

AF:

0.593

AC:

5101

ExAC

AF:

0.621

AC:

75330

Asia WGS

AF:

0.703

AC:

2444

AN:

3478

EpiCase

AF:

0.609

EpiControl

AF:

0.607

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Primary ciliary dyskinesia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 07, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Primary ciliary dyskinesia 18

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.030

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.14

T;T

MetaRNN

Benign

0.0000047

T;T

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.44

PROVEAN

Benign

1.6

N;N

REVEL

Benign

0.072

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.032

MPC

0.16

ClinPred

0.00081

GERP RS

2.8

Varity_R

0.057

gMVP

0.085

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