rs112051327

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_StrongBS1BS2

The NM_178452.6(DNAAF1):c.780G>C(p.Gln260His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,613,980 control chromosomes in the GnomAD database, including 74 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 45 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 29 hom. )

Consequence

DNAAF1
NM_178452.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.169

Publications

3 publications found

Variant links:

Genes affected

DNAAF1 (HGNC:30539): (dynein axonemal assembly factor 1) The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

DNAAF1 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 13
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAAF1 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=0.002643168).

BP6

Variant 16-84159713-G-C is Benign according to our data. Variant chr16-84159713-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0119 (1818/152306) while in subpopulation AFR AF = 0.0418 (1735/41552). AF 95% confidence interval is 0.0401. There are 45 homozygotes in GnomAd4. There are 838 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 45 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178452.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF1	NM_178452.6	MANE Select	c.780G>C	p.Gln260His	missense	Exon 6 of 12	NP_848547.4
	DNAAF1	NM_001318756.1		c.24G>C	p.Gln8His	missense	Exon 2 of 8	NP_001305685.1	Q8NEP3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAAF1	ENST00000378553.10	TSL:1 MANE Select	c.780G>C	p.Gln260His	missense	Exon 6 of 12	ENSP00000367815.5	Q8NEP3-1
DNAAF1	ENST00000567918.5	TSL:1	n.*99G>C		non_coding_transcript_exon	Exon 7 of 7	ENSP00000455154.1	H3BP51
DNAAF1	ENST00000567918.5	TSL:1	n.*99G>C		3_prime_UTR	Exon 7 of 7	ENSP00000455154.1	H3BP51

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1811

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0417

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

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:

0.000235

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.00300

AC:

753

AN:

251308

AF XY:

0.00209

show subpopulations

Gnomad AFR exome

AF:

0.0406

Gnomad AMR exome

AF:

0.00211

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.00120

AC:

1761

AN:

1461674

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

753

AN XY:

727132

show subpopulations

African (AFR)

AF:

0.0417

AC:

1396

AN:

33468

American (AMR)

AF:

0.00241

AC:

108

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00312

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000648

AC:

AN:

1111894

Other (OTH)

AF:

0.00272

AC:

164

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

173

259

346

432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.0119

AC:

1818

AN:

152306

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

838

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0418

AC:

1735

AN:

41552

American (AMR)

AF:

0.00301

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68032

Other (OTH)

AF:

0.00994

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

166

250

333

416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00187

Hom.:

Bravo

AF:

0.0131

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0350

AC:

154

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00352

AC:

427

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia 13 (3)

not provided (2)

not specified (2)

Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.14

(source)

DANN

Benign

0.097

DEOGEN2

Benign

0.0012

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

PhyloP100

-0.17

PrimateAI

Benign

0.30

PROVEAN

Benign

0.42

REVEL

Benign

0.011

Sift

Benign

1.0

Sift4G

Benign

0.45

Polyphen

0.0

Vest4

0.16

MutPred

0.33

Loss of MoRF binding (P = 0.1095)

MVP

0.055

MPC

0.019

ClinPred

0.00066

GERP RS

-2.9

Varity_R

0.048

gMVP

0.27

Mutation Taster

=94/6

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over