14-49633965-C-G

Position:

chr14-49633965-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018139.3(DNAAF2):c.1185G>C(p.Ala395=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 1,527,492 control chromosomes in the GnomAD database, including 415,888 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 39476 hom., cov: 33)

Exomes 𝑓: 0.73 ( 376412 hom. )

Consequence

DNAAF2
NM_018139.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.81

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]

DNAAF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 14-49633965-C-G is Benign according to our data. Variant chr14-49633965-C-G is described in ClinVar as [Benign]. Clinvar id is 95891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-49633965-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.81 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DNAAF2	NM_018139.3 linkuse as main transcript	c.1185G>C	p.Ala395=	synonymous_variant	1/3	ENST00000298292.13	NP_060609.2
DNAAF2	NM_001083908.2 linkuse as main transcript	c.1185G>C	p.Ala395=	synonymous_variant	1/2		NP_001077377.1
DNAAF2	NM_001378453.1 linkuse as main transcript	c.-687G>C		5_prime_UTR_variant	1/2		NP_001365382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF2	ENST00000298292.13 linkuse as main transcript	c.1185G>C	p.Ala395=	synonymous_variant	1/3	1	NM_018139.3	ENSP00000298292	P2	Q9NVR5-1
DNAAF2	ENST00000406043.3 linkuse as main transcript	c.1185G>C	p.Ala395=	synonymous_variant	1/2	1		ENSP00000384862	A2	Q9NVR5-2

Frequencies

GnomAD3 genomes

AF:

0.709

AC:

107811

AN:

151974

Hom.:

39446

Cov.:

show subpopulations

Gnomad AFR

AF:

0.692

Gnomad AMI

AF:

0.828

Gnomad AMR

AF:

0.691

Gnomad ASJ

AF:

0.728

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.795

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.763

Gnomad OTH

AF:

0.710

GnomAD3 exomes

AF:

0.644

AC:

79450

AN:

123412

Hom.:

27395

AF XY:

0.641

AC XY:

43385

AN XY:

67704

show subpopulations

Gnomad AFR exome

AF:

0.686

Gnomad AMR exome

AF:

0.628

Gnomad ASJ exome

AF:

0.728

Gnomad EAS exome

AF:

0.147

Gnomad SAS exome

AF:

0.551

Gnomad FIN exome

AF:

0.774

Gnomad NFE exome

AF:

0.764

Gnomad OTH exome

AF:

0.691

GnomAD4 exome

AF:

0.730

AC:

1004113

AN:

1375408

Hom.:

376412

Cov.:

AF XY:

0.725

AC XY:

491876

AN XY:

678326

show subpopulations

Gnomad4 AFR exome

AF:

0.681

Gnomad4 AMR exome

AF:

0.637

Gnomad4 ASJ exome

AF:

0.736

Gnomad4 EAS exome

AF:

0.118

Gnomad4 SAS exome

AF:

0.548

Gnomad4 FIN exome

AF:

0.772

Gnomad4 NFE exome

AF:

0.768

Gnomad4 OTH exome

AF:

0.695

GnomAD4 genome

AF:

0.709

AC:

107891

AN:

152084

Hom.:

39476

Cov.:

AF XY:

0.705

AC XY:

52424

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.692

Gnomad4 AMR

AF:

0.691

Gnomad4 ASJ

AF:

0.728

Gnomad4 EAS

AF:

0.147

Gnomad4 SAS

AF:

0.533

Gnomad4 FIN

AF:

0.795

Gnomad4 NFE

AF:

0.763

Gnomad4 OTH

AF:

0.709

Alfa

AF:

0.695

Hom.:

4655

Bravo

AF:

0.700

Asia WGS

AF:

0.405

AC:

1403

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 22, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Ala395Ala in exon 1 of DNAAF2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 81.2% (138/170) of European American chromosomes from a broad population by the 1000 Genomes Projec t (http://www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs2985686). -

Primary ciliary dyskinesia 10

Benign:3

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Primary ciliary dyskinesia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Nov 26, 2014	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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.50

DANN

Benign

0.61

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over