GeneBe

rs147110554

Positions:

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1

The NM_018139.3(DNAAF2):ā€‹c.2187A>Gā€‹(p.Gln729=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00024 in 1,612,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.00093 ( 0 hom., cov: 33)
Exomes š‘“: 0.00017 ( 0 hom. )

Consequence

DNAAF2
NM_018139.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.640
Variant links:
Genes affected
DNAAF2 (HGNC:20188): (dynein axonemal assembly factor 2) This gene encodes a highly conserved protein involved in the preassembly of dynein arm complexes which power cilia. These complexes are found in some cilia and are assembled in the cytoplasm prior to transport for cilia formation. Mutations in this gene have been associated with primary ciliary dyskinesia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 14-49625869-T-C is Benign according to our data. Variant chr14-49625869-T-C is described in ClinVar as [Benign]. Clinvar id is 215525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.64 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000932 (142/152338) while in subpopulation AFR AF= 0.0031 (129/41586). AF 95% confidence interval is 0.00267. There are 0 homozygotes in gnomad4. There are 67 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAAF2NM_018139.3 linkuse as main transcriptc.2187A>G p.Gln729= synonymous_variant 3/3 ENST00000298292.13 NP_060609.2
DNAAF2NM_001083908.2 linkuse as main transcriptc.2043A>G p.Gln681= synonymous_variant 2/2 NP_001077377.1
DNAAF2NM_001378453.1 linkuse as main transcriptc.-25A>G 5_prime_UTR_variant 2/2 NP_001365382.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAAF2ENST00000298292.13 linkuse as main transcriptc.2187A>G p.Gln729= synonymous_variant 3/31 NM_018139.3 ENSP00000298292 P2Q9NVR5-1
DNAAF2ENST00000406043.3 linkuse as main transcriptc.2043A>G p.Gln681= synonymous_variant 2/21 ENSP00000384862 A2Q9NVR5-2

Frequencies

GnomAD3 genomes
AF:
0.000933
AC:
142
AN:
152220
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00311
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000655
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:
0.0000294
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000337
AC:
84
AN:
249358
Hom.:
0
AF XY:
0.000223
AC XY:
30
AN XY:
134730
show subpopulations
Gnomad AFR exome
AF:
0.00340
Gnomad AMR exome
AF:
0.000584
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000708
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000168
AC:
245
AN:
1460212
Hom.:
0
Cov.:
32
AF XY:
0.000140
AC XY:
102
AN XY:
726300
show subpopulations
Gnomad4 AFR exome
AF:
0.00380
Gnomad4 AMR exome
AF:
0.000539
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000612
Gnomad4 OTH exome
AF:
0.000315
GnomAD4 genome
AF:
0.000932
AC:
142
AN:
152338
Hom.:
0
Cov.:
33
AF XY:
0.000899
AC XY:
67
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.00310
Gnomad4 AMR
AF:
0.000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00103
Hom.:
0
Bravo
AF:
0.00124
Asia WGS
AF:
0.000578
AC:
2
AN:
3476
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 13, 2024- -
Benign, criteria provided, single submitterclinical testingAmbry GeneticsAug 10, 2018This 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
1.8
DANN
Benign
0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147110554; hg19: chr14-50092587; API