rs2293979

Variant names:

Your query was ambiguous. Multiple possible variants found:

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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012472.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAAF11	NM_012472.6	MANE Select	c.695C>T	p.Thr232Ile	missense	Exon 6 of 12	NP_036604.2
DNAAF11	NM_001321961.2		c.695C>T	p.Thr232Ile	missense	Exon 6 of 11	NP_001308890.1
DNAAF11	NM_001321962.2		c.449C>T	p.Thr150Ile	missense	Exon 4 of 10	NP_001308891.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAAF11	ENST00000620350.5	TSL:1 MANE Select	c.695C>T	p.Thr232Ile	missense	Exon 6 of 12	ENSP00000484634.1	Q86X45-1
DNAAF11	ENST00000519595.5	TSL:1	c.695C>T	p.Thr232Ile	missense	Exon 6 of 12	ENSP00000429791.1	Q86X45-1
DNAAF11	ENST00000250173.5	TSL:1	c.695C>T	p.Thr232Ile	missense	Exon 6 of 13	ENSP00000250173.2	G5EA20

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia 19 (4)

not provided (2)

not specified (2)

Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

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

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.17

MetaRNN

Benign

9.4e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.83

PhyloP100

-2.9

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.060

REVEL

Benign

0.023

Sift

Benign

0.47

Sift4G

Benign

0.20

Polyphen

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over