Genetic Variant DNAAF10:p.Arg266Gln (chr2-68134771-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138458.4(DNAAF10):c.797G>A(p.Arg266Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,611,182 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

DNAAF10
NM_138458.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05

Variant links:

Genes affected

DNAAF10 (HGNC:25176): (dynein axonemal assembly factor 10) This gene encodes a protein with two WD40 repeat domains thought to be involved in an apoptosis via activation of caspase-3. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

DNAAF10 links:

ENSG00000273398 (HGNC:):

ENSG00000273398 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF10	NM_138458.4 link	c.797G>A	p.Arg266Gln	missense_variant	Exon 7 of 8	ENST00000295121.11	NP_612467.1	Q96MX6-1A0A140VK67
DNAAF10	NM_001256476.2 link	c.797G>A	p.Arg266Gln	missense_variant	Exon 7 of 7		NP_001243405.1	Q96MX6-2
DNAAF10	NR_046234.2 link	n.768G>A		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAAF10	ENST00000295121.11 link	c.797G>A	p.Arg266Gln	missense_variant	Exon 7 of 8	1	NM_138458.4	ENSP00000295121.6	Q96MX6-1
ENSG00000273398	ENST00000406334.3 link	n.*814G>A		non_coding_transcript_exon_variant	Exon 14 of 15	2		ENSP00000384974.3	H7BYZ3
ENSG00000273398	ENST00000406334.3 link	n.*814G>A		3_prime_UTR_variant	Exon 14 of 15	2		ENSP00000384974.3	H7BYZ3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459034

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725852

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:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.797G>A (p.R266Q) alteration is located in exon 7 (coding exon 7) of the WDR92 gene. This alteration results from a G to A substitution at nucleotide position 797, causing the arginine (R) at amino acid position 266 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.011

T;.;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.047

MetaRNN

Uncertain

0.55

D;D;D

MetaSVM

Uncertain

0.062

MutationAssessor

Uncertain

2.5

M;.;M

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-2.3

N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.054

T;T;T

Sift4G

Benign

0.23

T;T;T

Polyphen

0.92

P;.;.

Vest4

0.79

MutPred

0.62

Loss of MoRF binding (P = 0.0144);.;Loss of MoRF binding (P = 0.0144);

MVP

0.69

MPC

0.39

ClinPred

0.97

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.53

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