rs2293979

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012472.6(DNAAF11):c.695C>T(p.Thr232Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 1,610,902 control chromosomes in the GnomAD database, including 152,357 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 22834 hom., cov: 32)

Exomes 𝑓: 0.41 ( 129523 hom. )

Consequence

DNAAF11
NM_012472.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -2.93

Variant links:

Genes affected

DNAAF11 (HGNC:16725): (dynein axonemal assembly factor 11) The protein encoded by this gene contains several leucine-rich repeat domains and appears to be involved in the motility of cilia. Defects in this gene are a cause of primary ciliary dyskinesia-19 (CILD19). Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 4, 11 and 22. [provided by RefSeq, Apr 2016]

DNAAF11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.4263197E-7).

BP6

Variant 8-132625413-G-A is Benign according to our data. Variant chr8-132625413-G-A is described in ClinVar as [Benign]. Clinvar id is 260278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-132625413-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF11	NM_012472.6 linkuse as main transcript	c.695C>T	p.Thr232Ile	missense_variant	6/12	ENST00000620350.5	NP_036604.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF11	ENST00000620350.5 linkuse as main transcript	c.695C>T	p.Thr232Ile	missense_variant	6/12	1	NM_012472.6	ENSP00000484634	P1	Q86X45-1

Frequencies

GnomAD3 genomes

AF:

0.507

AC:

77019

AN:

151880

Hom.:

22781

Cov.:

show subpopulations

Gnomad AFR

AF:

0.830

Gnomad AMI

AF:

0.288

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.375

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.412

Gnomad OTH

AF:

0.482

GnomAD3 exomes

AF:

0.401

AC:

100198

AN:

249622

Hom.:

22499

AF XY:

0.402

AC XY:

54221

AN XY:

134884

show subpopulations

Gnomad AFR exome

AF:

0.840

Gnomad AMR exome

AF:

0.241

Gnomad ASJ exome

AF:

0.375

Gnomad EAS exome

AF:

0.297

Gnomad SAS exome

AF:

0.419

Gnomad FIN exome

AF:

0.337

Gnomad NFE exome

AF:

0.413

Gnomad OTH exome

AF:

0.405

GnomAD4 exome

AF:

0.412

AC:

601037

AN:

1458904

Hom.:

129523

Cov.:

AF XY:

0.412

AC XY:

298992

AN XY:

725784

show subpopulations

Gnomad4 AFR exome

AF:

0.840

Gnomad4 AMR exome

AF:

0.254

Gnomad4 ASJ exome

AF:

0.373

Gnomad4 EAS exome

AF:

0.228

Gnomad4 SAS exome

AF:

0.420

Gnomad4 FIN exome

AF:

0.345

Gnomad4 NFE exome

AF:

0.415

Gnomad4 OTH exome

AF:

0.425

GnomAD4 genome

AF:

0.507

AC:

77133

AN:

151998

Hom.:

22834

Cov.:

AF XY:

0.499

AC XY:

37029

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.830

Gnomad4 AMR

AF:

0.331

Gnomad4 ASJ

AF:

0.375

Gnomad4 EAS

AF:

0.280

Gnomad4 SAS

AF:

0.417

Gnomad4 FIN

AF:

0.334

Gnomad4 NFE

AF:

0.412

Gnomad4 OTH

AF:

0.489

Alfa

AF:

0.421

Hom.:

36471

Bravo

AF:

0.517

TwinsUK

AF:

0.405

AC:

1501

ALSPAC

AF:

0.413

AC:

1590

ESP6500AA

AF:

0.818

AC:

3606

ESP6500EA

AF:

0.425

AC:

3654

ExAC

AF:

0.418

AC:

50696

Asia WGS

AF:

0.383

AC:

1335

AN:

3478

EpiCase

AF:

0.408

EpiControl

AF:

0.408

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 19

Benign:4

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	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 -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 07, 2016	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.0040

DANN

Benign

0.53

DEOGEN2

Benign

0.0036

.;T;T;T;T

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.17

T;T;.;.;T

MetaRNN

Benign

9.4e-7

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.83

.;N;N;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.060

.;.;N;N;N

REVEL

Benign

0.023

Sift

Benign

0.47

.;.;T;T;T

Sift4G

Benign

0.20

T;T;T;T;T

Polyphen

0.0

.;B;B;.;.

Vest4

0.013

MPC

0.073

ClinPred

0.015

GERP RS

-9.6

Varity_R

0.022

gMVP

0.16

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