Variant rs759671132 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000297440.11(DNAAF5):c.2075C>G(p.Ala692Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A692V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DNAAF5
ENST00000297440.11 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.409

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05845833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DNAAF5	NM_017802.4 linkuse as main transcript	c.2075C>G	p.Ala692Gly	missense_variant	10/13	ENST00000297440.11	NP_060272.3
DNAAF5	XM_024446813.2 linkuse as main transcript	c.2075C>G	p.Ala692Gly	missense_variant	10/12		XP_024302581.1
DNAAF5	NR_075098.2 linkuse as main transcript	n.2035C>G		non_coding_transcript_exon_variant	10/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF5	ENST00000297440.11 linkuse as main transcript	c.2075C>G	p.Ala692Gly	missense_variant	10/13	1	NM_017802.4	ENSP00000297440	P1	Q86Y56-1
DNAAF5	ENST00000403952.3 linkuse as main transcript	c.350C>G	p.Ala117Gly	missense_variant	3/6	1		ENSP00000384884
DNAAF5	ENST00000440747.5 linkuse as main transcript	c.1481C>G	p.Ala494Gly	missense_variant	10/13	2		ENSP00000403165

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000830

AC:

AN:

240956

Hom.:

AF XY:

0.00000762

AC XY:

AN XY:

131152

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000184

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1454830

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723990

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000166

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.054

T;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.027

Sift

Benign

0.40

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.30

B;B

Vest4

0.18

MutPred

0.28

Gain of relative solvent accessibility (P = 0.0479);.;

MVP

0.040

MPC

0.16

ClinPred

0.076

GERP RS

2.6

Varity_R

0.029

gMVP

0.090

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over