Variant 14-49625214-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018139.3(DNAAF2):c.*328A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 157,910 control chromosomes in the GnomAD database, including 39,697 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 38198 hom., cov: 32)

Exomes 𝑓: 0.69 ( 1499 hom. )

Consequence

DNAAF2
NM_018139.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.122

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 14-49625214-T-A is Benign according to our data. Variant chr14-49625214-T-A is described in ClinVar as [Benign]. Clinvar id is 313270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF2	NM_018139.3 linkuse as main transcript	c.*328A>T	3_prime_UTR_variant	3/3	ENST00000298292.13	NP_060609.2	Q9NVR5-1
DNAAF2	NM_001083908.2 linkuse as main transcript	c.*328A>T	3_prime_UTR_variant	2/2		NP_001077377.1	Q9NVR5-2
DNAAF2	NM_001378453.1 linkuse as main transcript	c.*328A>T	3_prime_UTR_variant	2/2		NP_001365382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF2	ENST00000298292 linkuse as main transcript	c.*328A>T		3_prime_UTR_variant	3/3	1	NM_018139.3	ENSP00000298292.8		Q9NVR5-1
DNAAF2	ENST00000406043 linkuse as main transcript	c.*328A>T		3_prime_UTR_variant	2/2	1		ENSP00000384862.3		Q9NVR5-2

Frequencies

GnomAD3 genomes

AF:

0.697

AC:

105896

AN:

151886

Hom.:

38173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.649

Gnomad AMI

AF:

0.828

Gnomad AMR

AF:

0.687

Gnomad ASJ

AF:

0.728

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.795

Gnomad MID

AF:

0.726

Gnomad NFE

AF:

0.763

Gnomad OTH

AF:

0.701

GnomAD4 exome

AF:

0.687

AC:

4056

AN:

5906

Hom.:

1499

Cov.:

AF XY:

0.689

AC XY:

2067

AN XY:

3000

show subpopulations

Gnomad4 AFR exome

AF:

0.630

Gnomad4 AMR exome

AF:

0.659

Gnomad4 ASJ exome

AF:

0.745

Gnomad4 EAS exome

AF:

0.117

Gnomad4 SAS exome

AF:

0.463

Gnomad4 FIN exome

AF:

0.780

Gnomad4 NFE exome

AF:

0.755

Gnomad4 OTH exome

AF:

0.678

GnomAD4 genome

AF:

0.697

AC:

105970

AN:

152004

Hom.:

38198

Cov.:

AF XY:

0.693

AC XY:

51494

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.649

Gnomad4 AMR

AF:

0.687

Gnomad4 ASJ

AF:

0.728

Gnomad4 EAS

AF:

0.148

Gnomad4 SAS

AF:

0.533

Gnomad4 FIN

AF:

0.795

Gnomad4 NFE

AF:

0.763

Gnomad4 OTH

AF:

0.700

Alfa

AF:

0.722

Hom.:

5016

Bravo

AF:

0.685

Asia WGS

AF:

0.399

AC:

1370

AN:

3438

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Congenital disorder of glycosylation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

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

-0.87

CADD

Benign

3.0

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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