chr8-132625413-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

35 publications found

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 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 19
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen

DNAAF11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 260278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF11	NM_012472.6 link	c.695C>T	p.Thr232Ile	missense_variant	Exon 6 of 12	ENST00000620350.5	NP_036604.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF11	ENST00000620350.5 link	c.695C>T	p.Thr232Ile	missense_variant	Exon 6 of 12	1	NM_012472.6	ENSP00000484634.1

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

GnomAD2 exomes

AF:

0.401

AC:

100198

AN:

249622

AF XY:

0.402

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 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

African (AFR)

AF:

0.840

AC:

28072

AN:

33430

American (AMR)

AF:

0.254

AC:

11310

AN:

44560

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

9726

AN:

26100

East Asian (EAS)

AF:

0.228

AC:

9019

AN:

39634

South Asian (SAS)

AF:

0.420

AC:

36071

AN:

85836

European-Finnish (FIN)

AF:

0.345

AC:

18424

AN:

53382

Middle Eastern (MID)

AF:

0.427

AC:

2460

AN:

5760

European-Non Finnish (NFE)

AF:

0.415

AC:

460340

AN:

1109896

Other (OTH)

AF:

0.425

AC:

25615

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

15686

31371

47057

62742

78428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14128

28256

42384

56512

70640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.507

AC:

77133

AN:

151998

Hom.:

22834

Cov.:

AF XY:

0.499

AC XY:

37029

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.830

AC:

34416

AN:

41474

American (AMR)

AF:

0.331

AC:

5061

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

1299

AN:

3464

East Asian (EAS)

AF:

0.280

AC:

1443

AN:

5154

South Asian (SAS)

AF:

0.417

AC:

2004

AN:

4810

European-Finnish (FIN)

AF:

0.334

AC:

3531

AN:

10564

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.412

AC:

27980

AN:

67936

Other (OTH)

AF:

0.489

AC:

1032

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1638

3276

4915

6553

8191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.439

Hom.:

62319

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 -

Primary ciliary dyskinesia

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 07, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Nov 12, 2018

GeneDx

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

- -

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

(source)

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;.;.

PhyloP100

-2.9

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

PromoterAI

-0.0042

Neutral

(source)

Varity_R

0.022

gMVP

0.16

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over