Genetic Variant DNAAF11:p.Thr232Lys (chr8-132625413-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_012472.6(DNAAF11):c.695C>A(p.Thr232Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T232I) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

DNAAF11
NM_012472.6 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031152725).

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>A	p.Thr232Lys	missense	Exon 6 of 12	NP_036604.2
DNAAF11	NM_001321961.2		c.695C>A	p.Thr232Lys	missense	Exon 6 of 11	NP_001308890.1
DNAAF11	NM_001321962.2		c.449C>A	p.Thr150Lys	missense	Exon 4 of 10	NP_001308891.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAAF11	ENST00000620350.5	TSL:1 MANE Select	c.695C>A	p.Thr232Lys	missense	Exon 6 of 12	ENSP00000484634.1
DNAAF11	ENST00000519595.5	TSL:1	c.695C>A	p.Thr232Lys	missense	Exon 6 of 12	ENSP00000429791.1
DNAAF11	ENST00000250173.5	TSL:1	c.695C>A	p.Thr232Lys	missense	Exon 6 of 13	ENSP00000250173.2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151940

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151940

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74180

African (AFR)

AF:

0.00

AC:

AN:

41372

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67964

Other (OTH)

AF:

0.00

AC:

AN:

2090

Alfa

AF:

0.00

Hom.:

62319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.0020

(source)

DANN

Benign

0.15

DEOGEN2

Benign

0.0025

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.0085

LIST_S2

Benign

0.16

M_CAP

Benign

0.0049

MetaRNN

Benign

0.031

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.35

PhyloP100

-2.9

PrimateAI

Benign

0.25

PROVEAN

Benign

0.11

REVEL

Benign

0.0040

Sift

Benign

0.61

Sift4G

Benign

0.92

Polyphen

0.0

Vest4

0.059

MutPred

0.33

Gain of ubiquitination at T232 (P = 9e-04)

MVP

0.040

MPC

0.082

ClinPred

0.042

GERP RS

-9.6

PromoterAI

0.0087

Neutral

(source)

Varity_R

0.037

gMVP

0.26

Mutation Taster

=96/4

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over