chr8-132572310-A-G

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.1397T>C(p.Ile466Thr) variant causes a missense change. The variant allele was found at a frequency of 0.1 in 1,611,468 control chromosomes in the GnomAD database, including 10,570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2573 hom., cov: 32)

Exomes 𝑓: 0.095 ( 7997 hom. )

Consequence

DNAAF11
NM_012472.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 5.93

Publications

17 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=0.0019569993).

BP6

Variant 8-132572310-A-G is Benign according to our data. Variant chr8-132572310-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 260274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF11	NM_012472.6 link	c.1397T>C	p.Ile466Thr	missense_variant	Exon 12 of 12	ENST00000620350.5	NP_036604.2	Q86X45-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF11	ENST00000620350.5 link	c.1397T>C	p.Ile466Thr	missense_variant	Exon 12 of 12	1	NM_012472.6	ENSP00000484634.1		Q86X45-1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22926

AN:

152032

Hom.:

2568

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.0878

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.0397

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.0558

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0924

Gnomad OTH

AF:

0.149

GnomAD2 exomes

AF:

0.0991

AC:

24690

AN:

249022

AF XY:

0.0986

show subpopulations

Gnomad AFR exome

AF:

0.315

Gnomad AMR exome

AF:

0.0542

Gnomad ASJ exome

AF:

0.109

Gnomad EAS exome

AF:

0.0459

Gnomad FIN exome

AF:

0.0592

Gnomad NFE exome

AF:

0.0939

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.0952

AC:

138902

AN:

1459320

Hom.:

7997

Cov.:

AF XY:

0.0958

AC XY:

69526

AN XY:

725958

show subpopulations

African (AFR)

AF:

0.329

AC:

10949

AN:

33244

American (AMR)

AF:

0.0601

AC:

2660

AN:

44274

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

2797

AN:

26000

East Asian (EAS)

AF:

0.0306

AC:

1212

AN:

39666

South Asian (SAS)

AF:

0.114

AC:

9728

AN:

85704

European-Finnish (FIN)

AF:

0.0638

AC:

3402

AN:

53356

Middle Eastern (MID)

AF:

0.117

AC:

674

AN:

5756

European-Non Finnish (NFE)

AF:

0.0910

AC:

101096

AN:

1111040

Other (OTH)

AF:

0.106

AC:

6384

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

5995

11989

17984

23978

29973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.151

AC:

22943

AN:

152148

Hom.:

2573

Cov.:

AF XY:

0.147

AC XY:

10924

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.317

AC:

13148

AN:

41446

American (AMR)

AF:

0.0876

AC:

1340

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

379

AN:

3472

East Asian (EAS)

AF:

0.0396

AC:

205

AN:

5174

South Asian (SAS)

AF:

0.109

AC:

525

AN:

4820

European-Finnish (FIN)

AF:

0.0558

AC:

592

AN:

10612

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0924

AC:

6282

AN:

68010

Other (OTH)

AF:

0.147

AC:

311

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

902

1804

2705

3607

4509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.113

Hom.:

4954

Bravo

AF:

0.160

TwinsUK

AF:

0.0898

AC:

333

ALSPAC

AF:

0.0947

AC:

365

ESP6500AA

AF:

0.294

AC:

1297

ESP6500EA

AF:

0.0967

AC:

832

ExAC

AF:

0.105

AC:

12803

Asia WGS

AF:

0.0850

AC:

301

AN:

3476

EpiCase

AF:

0.0928

EpiControl

AF:

0.0995

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 19

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Primary ciliary dyskinesia

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 08, 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:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.099

.;T;T;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.91

D;D;.;D

MetaRNN

Benign

0.0020

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

.;M;M;.

PhyloP100

5.9

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.4

.;.;N;N

REVEL

Benign

0.22

Sift

Uncertain

0.0030

.;.;D;D

Sift4G

Uncertain

0.0040

D;D;D;D

Polyphen

0.97

.;D;D;.

Vest4

0.14

ClinPred

0.027

GERP RS

5.7

Varity_R

0.15

gMVP

0.24

Mutation Taster

=94/6

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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chr8-132572310-A-G

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