Variant rs192289643 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_017802.4(DNAAF5):c.1394G>A(p.Arg465Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000316 in 1,610,722 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00031 ( 4 hom. )

Consequence

DNAAF5
NM_017802.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.10

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047600567).

BP6

Variant 7-756918-G-A is Benign according to our data. Variant chr7-756918-G-A is described in ClinVar as [Benign]. Clinvar id is 454852.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00042 (64/152344) while in subpopulation EAS AF= 0.0118 (61/5182). AF 95% confidence interval is 0.00941. There are 0 homozygotes in gnomad4. There are 38 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	HGVSp	Effect	#exon/exons	MANE	Protein
DNAAF5	NM_017802.4 linkuse as main transcript	c.1394G>A	p.Arg465Gln	missense_variant	6/13	ENST00000297440.11	NP_060272.3
DNAAF5	XM_024446813.2 linkuse as main transcript	c.1394G>A	p.Arg465Gln	missense_variant	6/12		XP_024302581.1
DNAAF5	NR_075098.2 linkuse as main transcript	n.1354G>A		non_coding_transcript_exon_variant	6/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF5	ENST00000297440.11 linkuse as main transcript	c.1394G>A	p.Arg465Gln	missense_variant	6/13	1	NM_017802.4	ENSP00000297440	P1	Q86Y56-1
DNAAF5	ENST00000440747.5 linkuse as main transcript	c.800G>A	p.Arg267Gln	missense_variant	6/13	2		ENSP00000403165

Frequencies

GnomAD3 genomes

AF:

0.000420

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0117

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000938

AC:

233

AN:

248498

Hom.:

AF XY:

0.00102

AC XY:

137

AN XY:

134750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0120

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0000996

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000305

AC:

445

AN:

1458378

Hom.:

Cov.:

AF XY:

0.000303

AC XY:

220

AN XY:

725632

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00952

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.0000799

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.000420

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0118

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000460

Hom.:

Bravo

AF:

0.000491

ExAC

AF:

0.000807

AC:

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0048

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.7

REVEL

Benign

0.11

Sift

Benign

0.19

Sift4G

Benign

0.16

Polyphen

0.54

Vest4

0.20

MVP

0.048

MPC

0.20

ClinPred

0.021

GERP RS

4.6

Varity_R

0.043

gMVP

0.11

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