Variant 2-68131428-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_138458.4(DNAAF10):c.884G>A(p.Arg295Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DNAAF10
NM_138458.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.50

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.786

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF10	NM_138458.4 linkuse as main transcript	c.884G>A	p.Arg295Gln	missense_variant	8/8	ENST00000295121.11	NP_612467.1	Q96MX6-1A0A140VK67

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAAF10	ENST00000295121.11 linkuse as main transcript	c.884G>A	p.Arg295Gln	missense_variant	8/8	1	NM_138458.4	ENSP00000295121.6	Q96MX6-1
ENSG00000273398	ENST00000406334.3 linkuse as main transcript	n.*901G>A		non_coding_transcript_exon_variant	15/15	2		ENSP00000384974.3	H7BYZ3
ENSG00000273398	ENST00000406334.3 linkuse as main transcript	n.*901G>A		3_prime_UTR_variant	15/15	2		ENSP00000384974.3	H7BYZ3
DNAAF10	ENST00000492039.6 linkuse as main transcript	n.874G>A		non_coding_transcript_exon_variant	8/10	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251236

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135796

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727226

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.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.884G>A (p.R295Q) alteration is located in exon 8 (coding exon 8) of the WDR92 gene. This alteration results from a G to A substitution at nucleotide position 884, causing the arginine (R) at amino acid position 295 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

Pathogenic

0.63

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.062

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.24

MetaRNN

Pathogenic

0.79

MetaSVM

Pathogenic

0.93

MutationAssessor

Pathogenic

3.4

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.8

REVEL

Pathogenic

0.76

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.66

MutPred

0.61

Gain of ubiquitination at K297 (P = 0.0551);

MVP

0.82

MPC

1.0

ClinPred

1.0

GERP RS

5.8

Varity_R

0.79

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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