rs2985684

Positions:

• chr14-49634964-C-A
• chr14-49634964-C-G
• chr14-49634964-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018139.3(DNAAF2):​c.186G>T​(p.Glu62Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000355 in 1,408,246 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. Another nucleotide change resulting in same amino acid change has been previously reported as Benignin Lovd.

• Frequency:
  • Genomes: not found (cov: 36)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: DNAAF2 NM_018139.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39216754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF2	NM_018139.3	c.186G>T	p.Glu62Asp	missense_variant	1/3	ENST00000298292.13	NP_060609.2
DNAAF2	NM_001083908.2	c.186G>T	p.Glu62Asp	missense_variant	1/2		NP_001077377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF2	ENST00000298292.13	c.186G>T	p.Glu62Asp	missense_variant	1/3	1	NM_018139.3	ENSP00000298292.8
DNAAF2	ENST00000406043.3	c.186G>T	p.Glu62Asp	missense_variant	1/2	1		ENSP00000384862.3

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome AF: 0.00000355 AC: 5 AN: 1408246 Hom.: 0 Cov.: 111 AF XY: 0.00 AC XY: 0 AN XY: 695788

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: 0.00000461

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 36

Alfa AF: 0.0000257 Hom.: 10431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.075
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.077
Sift	Benign	0.087	T;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.44	B;P
Vest4		0.18
MutPred		0.33		Gain of catalytic residue at E66 (P = 0.0107);Gain of catalytic residue at E66 (P = 0.0107);
MVP		0.36
MPC		1.4
ClinPred		0.95	D
GERP RS		4.2
Varity_R		0.12
gMVP		0.70

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

Other links and lift over

dbSNP: rs2985684; hg19: chr14-50101682;