rs2985684

Variant names:

• chr14-49634964-C-A
• rs2985684
• NM_018139.3:c.186G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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 the same amino acid substitution has been previously reported as Benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. E62E) has been classified as Likely benign.

• 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
• Publications: 35 publications found

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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 10

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018139.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF2	NM_018139.3	MANE Select	c.186G>T	p.Glu62Asp	missense	Exon 1 of 3	NP_060609.2
	DNAAF2	NM_001083908.2		c.186G>T	p.Glu62Asp	missense	Exon 1 of 2	NP_001077377.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF2	ENST00000298292.13	TSL:1 MANE Select	c.186G>T	p.Glu62Asp	missense	Exon 1 of 3	ENSP00000298292.8
	DNAAF2	ENST00000406043.3	TSL:1	c.186G>T	p.Glu62Asp	missense	Exon 1 of 2	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

African (AFR) AF: 0.00 AC: 0 AN: 32042

American (AMR) AF: 0.00 AC: 0 AN: 37108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25296

East Asian (EAS) AF: 0.00 AC: 0 AN: 36430

South Asian (SAS) AF: 0.00 AC: 0 AN: 80208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00000461 AC: 5 AN: 1084546

Other (OTH) AF: 0.00 AC: 0 AN: 58320

GnomAD4 genome Cov.: 36

Alfa AF: 0.0000257 Hom.: 10431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.077
Sift	Benign	0.087	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.44	B
Vest4		0.18
MutPred		0.33		Gain of catalytic residue at E66 (P = 0.0107)
MVP		0.36
MPC		1.4
ClinPred		0.95	D
GERP RS		4.2
PromoterAI		0.033	Neutral
Varity_R		0.12
gMVP		0.70
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs2985684; hg19: chr14-50101682;