Variant chr14-49628195-C-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.1864-40G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 1,510,446 control chromosomes in the GnomAD database, including 407,156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 38278 hom., cov: 32)

Exomes 𝑓: 0.73 ( 368878 hom. )

Consequence

DNAAF2
NM_018139.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.228

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=-0.89).

BP6

Variant 14-49628195-C-A is Benign according to our data. Variant chr14-49628195-C-A is described in ClinVar as [Benign]. Clinvar id is 261017.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	MANE
DNAAF2	NM_018139.3 linkuse as main transcript	c.1864-40G>T	intron_variant	ENST00000298292.13
DNAAF2	NM_001083908.2 linkuse as main transcript	c.1864-2147G>T	intron_variant
DNAAF2	NM_001378453.1 linkuse as main transcript	c.-204-2147G>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF2	ENST00000298292.13 linkuse as main transcript	c.1864-40G>T		intron_variant		1	NM_018139.3	P2	Q9NVR5-1
DNAAF2	ENST00000406043.3 linkuse as main transcript	c.1864-2147G>T		intron_variant		1		A2	Q9NVR5-2

Frequencies

GnomAD3 genomes

AF:

0.698

AC:

106053

AN:

151982

Hom.:

38249

Cov.:

show subpopulations

Gnomad AFR

AF:

0.651

Gnomad AMI

AF:

0.828

Gnomad AMR

AF:

0.686

Gnomad ASJ

AF:

0.729

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.795

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.763

Gnomad OTH

AF:

0.702

GnomAD3 exomes

AF:

0.653

AC:

106925

AN:

163780

Hom.:

37232

AF XY:

0.649

AC XY:

56033

AN XY:

86364

show subpopulations

Gnomad AFR exome

AF:

0.631

Gnomad AMR exome

AF:

0.623

Gnomad ASJ exome

AF:

0.730

Gnomad EAS exome

AF:

0.148

Gnomad SAS exome

AF:

0.545

Gnomad FIN exome

AF:

0.778

Gnomad NFE exome

AF:

0.754

Gnomad OTH exome

AF:

0.687

GnomAD4 exome

AF:

0.727

AC:

986851

AN:

1358348

Hom.:

368878

Cov.:

AF XY:

0.722

AC XY:

485326

AN XY:

672304

show subpopulations

Gnomad4 AFR exome

AF:

0.641

Gnomad4 AMR exome

AF:

0.631

Gnomad4 ASJ exome

AF:

0.736

Gnomad4 EAS exome

AF:

0.118

Gnomad4 SAS exome

AF:

0.546

Gnomad4 FIN exome

AF:

0.775

Gnomad4 NFE exome

AF:

0.767

Gnomad4 OTH exome

AF:

0.691

GnomAD4 genome

AF:

0.698

AC:

106132

AN:

152098

Hom.:

38278

Cov.:

AF XY:

0.694

AC XY:

51585

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.651

Gnomad4 AMR

AF:

0.687

Gnomad4 ASJ

AF:

0.729

Gnomad4 EAS

AF:

0.148

Gnomad4 SAS

AF:

0.533

Gnomad4 FIN

AF:

0.795

Gnomad4 NFE

AF:

0.763

Gnomad4 OTH

AF:

0.701

Alfa

AF:

0.722

Hom.:

8214

Bravo

AF:

0.686

Asia WGS

AF:

0.401

AC:

1393

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.3

DANN

Benign

0.33

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