rs57809907

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBA1

The NM_130810.4(DNAAF4):c.1249G>T(p.Glu417*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,611,952 control chromosomes in the GnomAD database, including 13,397 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 4178 hom., cov: 32)

Exomes 𝑓: 0.096 ( 9219 hom. )

Consequence

DNAAF4
NM_130810.4 stop_gained

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 0.351

Variant links:

Genes affected

DNAAF4 (HGNC:21493): (dynein axonemal assembly factor 4) This gene encodes a tetratricopeptide repeat domain-containing protein. The encoded protein interacts with estrogen receptors and the heat shock proteins, Hsp70 and Hsp90. An homologous protein in rat has been shown to function in neuronal migration in the developing neocortex. A chromosomal translocation involving this gene is associated with a susceptibility to developmental dyslexia. Mutations in this gene are associated with deficits in reading and spelling. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream cell cycle progression 1 (CCPG1) gene. [provided by RefSeq, Mar 2011]

DNAAF4 links:

DNAAF4-CCPG1 (HGNC:43019): (DNAAF4-CCPG1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring dyslexia susceptibility 1 candidate 1 (DYX1C1) and cell cycle progression 1 (CCPG1) genes on chromosome 15. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

DNAAF4-CCPG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0111 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BP6

Variant 15-55430684-C-A is Benign according to our data. Variant chr15-55430684-C-A is described in ClinVar as [Benign]. Clinvar id is 2136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF4	NM_130810.4 link	c.1249G>T	p.Glu417*	stop_gained	Exon 10 of 10	ENST00000321149.7	NP_570722.2	Q8WXU2-1
DNAAF4	NM_001033559.3 link	c.*12G>T		3_prime_UTR_variant	Exon 9 of 9		NP_001028731.1	Q8WXU2-3
DNAAF4	NM_001033560.2 link	c.1047+4221G>T		intron_variant	Intron 8 of 8		NP_001028732.1	Q8WXU2-2A0A0S2Z5Z4
DNAAF4-CCPG1	NR_037923.1 link	n.1408+1813G>T		intron_variant	Intron 8 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7 link	c.1249G>T	p.Glu417*	stop_gained	Exon 10 of 10	1	NM_130810.4	ENSP00000323275.3		Q8WXU2-1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27025

AN:

151988

Hom.:

4172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.421

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.0108

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0849

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0852

Gnomad OTH

AF:

0.148

GnomAD3 exomes

AF:

0.104

AC:

26061

AN:

250812

Hom.:

2430

AF XY:

0.102

AC XY:

13830

AN XY:

135566

show subpopulations

Gnomad AFR exome

AF:

0.426

Gnomad AMR exome

AF:

0.0551

Gnomad ASJ exome

AF:

0.119

Gnomad EAS exome

AF:

0.00805

Gnomad SAS exome

AF:

0.126

Gnomad FIN exome

AF:

0.0793

Gnomad NFE exome

AF:

0.0860

Gnomad OTH exome

AF:

0.0962

GnomAD4 exome

AF:

0.0964

AC:

140755

AN:

1459846

Hom.:

9219

Cov.:

AF XY:

0.0965

AC XY:

70106

AN XY:

726294

show subpopulations

Gnomad4 AFR exome

AF:

0.438

Gnomad4 AMR exome

AF:

0.0612

Gnomad4 ASJ exome

AF:

0.124

Gnomad4 EAS exome

AF:

0.00551

Gnomad4 SAS exome

AF:

0.127

Gnomad4 FIN exome

AF:

0.0823

Gnomad4 NFE exome

AF:

0.0876

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.178

AC:

27065

AN:

152106

Hom.:

4178

Cov.:

AF XY:

0.175

AC XY:

13000

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.421

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.0108

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.0849

Gnomad4 NFE

AF:

0.0852

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.103

Hom.:

1862

Bravo

AF:

0.188

TwinsUK

AF:

0.0890

AC:

330

ALSPAC

AF:

0.0825

AC:

318

ESP6500AA

AF:

0.416

AC:

1825

ESP6500EA

AF:

0.0892

AC:

765

ExAC

AF:

0.112

AC:

13636

Asia WGS

AF:

0.0840

AC:

291

AN:

3474

EpiCase

AF:

0.0916

EpiControl

AF:

0.0925

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 23341075, 12954984, 31213628) -

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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, variant associated with dyslexia -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 25

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dyslexia, susceptibility to, 1

Other:1

Sep 30, 2003

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.59

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.33

Vest4

0.38

GERP RS

4.7

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