rs144077436

Variant names:

• chr14-49633566-A-C
• NM_018139.3:c.1584T>G

Your query was ambiguous. Multiple possible variants found:

• chr14-49633566-A-C
• chr14-49633566-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018139.3(DNAAF2):​c.1584T>G​(p.Asn528Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DNAAF2 NM_018139.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF2	NM_018139.3	c.1584T>G	p.Asn528Lys	missense_variant	Exon 1 of 3	ENST00000298292.13	NP_060609.2
DNAAF2	NM_001083908.2	c.1584T>G	p.Asn528Lys	missense_variant	Exon 1 of 2		NP_001077377.1
DNAAF2	NM_001378453.1	c.-288T>G		5_prime_UTR_variant	Exon 1 of 2		NP_001365382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF2	ENST00000298292.13	c.1584T>G	p.Asn528Lys	missense_variant	Exon 1 of 3	1	NM_018139.3	ENSP00000298292.8
DNAAF2	ENST00000406043.3	c.1584T>G	p.Asn528Lys	missense_variant	Exon 1 of 2	1		ENSP00000384862.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461674 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727120

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: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.084	T;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.50	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.028
Sift	Benign	0.050	D;D
Sift4G	Benign	0.091	T;T
Polyphen		0.42	B;P
Vest4		0.084
MutPred		0.45		Gain of catalytic residue at P523 (P = 0);Gain of catalytic residue at P523 (P = 0);
MVP		0.15
MPC		0.65
ClinPred		0.76	D
GERP RS		0.18
Varity_R		0.15
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.23		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-50100284;