rs7260371

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001256715.2(DNAAF3):​c.790-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,580,790 control chromosomes in the GnomAD database, including 25,997 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 6171 hom., cov: 32)
Exomes 𝑓: 0.15 ( 19826 hom. )

Consequence

DNAAF3
NM_001256715.2 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.698

Publications

5 publications found
Variant links:
Genes affected
DNAAF3 (HGNC:30492): (dynein axonemal assembly factor 3) The protein encoded by this gene is required for the assembly of axonemal inner and outer dynein arms and plays a role in assembling dynein complexes for transport into cilia. Defects in this gene are a cause of primary ciliary dyskinesia type 2 (CILD2). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]
DNAAF3-AS1 (HGNC:55292): (DNAAF3 antisense RNA 1)

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 (BayesDel_noAF=-0.8).
BP6
Variant 19-55161201-G-A is Benign according to our data. Variant chr19-55161201-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAAF3NM_001256715.2 linkc.790-14C>T intron_variant Intron 7 of 11 ENST00000524407.7 NP_001243644.1 Q8N9W5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAAF3ENST00000524407.7 linkc.790-14C>T intron_variant Intron 7 of 11 1 NM_001256715.2 ENSP00000432046.3 Q8N9W5-1

Frequencies

GnomAD3 genomes
AF:
0.239
AC:
36326
AN:
152062
Hom.:
6155
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.481
Gnomad AMI
AF:
0.145
Gnomad AMR
AF:
0.165
Gnomad ASJ
AF:
0.256
Gnomad EAS
AF:
0.0819
Gnomad SAS
AF:
0.136
Gnomad FIN
AF:
0.0986
Gnomad MID
AF:
0.294
Gnomad NFE
AF:
0.149
Gnomad OTH
AF:
0.239
GnomAD2 exomes
AF:
0.158
AC:
31552
AN:
199496
AF XY:
0.157
show subpopulations
Gnomad AFR exome
AF:
0.491
Gnomad AMR exome
AF:
0.112
Gnomad ASJ exome
AF:
0.251
Gnomad EAS exome
AF:
0.0767
Gnomad FIN exome
AF:
0.0973
Gnomad NFE exome
AF:
0.152
Gnomad OTH exome
AF:
0.191
GnomAD4 exome
AF:
0.154
AC:
220387
AN:
1428608
Hom.:
19826
Cov.:
39
AF XY:
0.153
AC XY:
108401
AN XY:
706786
show subpopulations
African (AFR)
AF:
0.495
AC:
16128
AN:
32590
American (AMR)
AF:
0.120
AC:
4868
AN:
40518
Ashkenazi Jewish (ASJ)
AF:
0.252
AC:
6423
AN:
25468
East Asian (EAS)
AF:
0.0516
AC:
1954
AN:
37894
South Asian (SAS)
AF:
0.137
AC:
11288
AN:
82574
European-Finnish (FIN)
AF:
0.105
AC:
5351
AN:
50922
Middle Eastern (MID)
AF:
0.289
AC:
1607
AN:
5552
European-Non Finnish (NFE)
AF:
0.148
AC:
162125
AN:
1094196
Other (OTH)
AF:
0.181
AC:
10643
AN:
58894
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.476
Heterozygous variant carriers
0
11857
23714
35570
47427
59284
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
5972
11944
17916
23888
29860
<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:
0.239
AC:
36388
AN:
152182
Hom.:
6171
Cov.:
32
AF XY:
0.231
AC XY:
17155
AN XY:
74424
show subpopulations
African (AFR)
AF:
0.482
AC:
19995
AN:
41508
American (AMR)
AF:
0.164
AC:
2510
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
0.256
AC:
890
AN:
3470
East Asian (EAS)
AF:
0.0817
AC:
422
AN:
5168
South Asian (SAS)
AF:
0.136
AC:
656
AN:
4826
European-Finnish (FIN)
AF:
0.0986
AC:
1047
AN:
10616
Middle Eastern (MID)
AF:
0.286
AC:
84
AN:
294
European-Non Finnish (NFE)
AF:
0.149
AC:
10144
AN:
67978
Other (OTH)
AF:
0.241
AC:
508
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1255
2510
3766
5021
6276
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
338
676
1014
1352
1690
<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:
0.203
Hom.:
771
Bravo
AF:
0.258
Asia WGS
AF:
0.164
AC:
569
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:12
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Mar 28, 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 -

-
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Primary ciliary dyskinesia 2 Benign:2
-
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

- -

Primary ciliary dyskinesia Benign:2
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Jul 09, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Dilated Cardiomyopathy, Recessive Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Hypertrophic cardiomyopathy Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Familial restrictive cardiomyopathy Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
7.5
DANN
Benign
0.86
PhyloP100
0.70
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs7260371; hg19: chr19-55672569; COSMIC: COSV61277233; COSMIC: COSV61277233; API