Variant 14-49625633-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018139.3(DNAAF2):c.2423A>G(p.Asn808Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DNAAF2
NM_018139.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.91

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18669441).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF2	NM_018139.3 linkuse as main transcript	c.2423A>G	p.Asn808Ser	missense_variant	3/3	ENST00000298292.13	NP_060609.2	Q9NVR5-1
DNAAF2	NM_001083908.2 linkuse as main transcript	c.2279A>G	p.Asn760Ser	missense_variant	2/2		NP_001077377.1	Q9NVR5-2
DNAAF2	NM_001378453.1 linkuse as main transcript	c.212A>G	p.Asn71Ser	missense_variant	2/2		NP_001365382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF2	ENST00000298292.13 linkuse as main transcript	c.2423A>G	p.Asn808Ser	missense_variant	3/3	1	NM_018139.3	ENSP00000298292.8		Q9NVR5-1
DNAAF2	ENST00000406043.3 linkuse as main transcript	c.2279A>G	p.Asn760Ser	missense_variant	2/2	1		ENSP00000384862.3		Q9NVR5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461388

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 27, 2023

The c.2423A>G (p.N808S) alteration is located in exon 3 (coding exon 3) of the DNAAF2 gene. This alteration results from a A to G substitution at nucleotide position 2423, causing the asparagine (N) at amino acid position 808 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

T;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.069

Sift

Benign

0.10

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.96

D;D

Vest4

0.14

MutPred

0.23

Gain of disorder (P = 0.0604);.;

MVP

0.40

MPC

0.98

ClinPred

0.83

GERP RS

5.9

Varity_R

0.061

gMVP

0.21

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over