rs771875922

Variant names:

• chr14-49634776-A-C
• NM_018139.3:c.374T>G

Your query was ambiguous. Multiple possible variants found:

• chr14-49634776-A-C
• chr14-49634776-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018139.3(DNAAF2):​c.374T>G​(p.Leu125Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,433,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DNAAF2 NM_018139.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.914

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF2	NM_018139.3	c.374T>G	p.Leu125Arg	missense_variant	Exon 1 of 3	ENST00000298292.13	NP_060609.2
DNAAF2	NM_001083908.2	c.374T>G	p.Leu125Arg	missense_variant	Exon 1 of 2		NP_001077377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF2	ENST00000298292.13	c.374T>G	p.Leu125Arg	missense_variant	Exon 1 of 3	1	NM_018139.3	ENSP00000298292.8
DNAAF2	ENST00000406043.3	c.374T>G	p.Leu125Arg	missense_variant	Exon 1 of 2	1		ENSP00000384862.3

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1433590 Hom.: 0 Cov.: 98 AF XY: 0.00 AC XY: 0 AN XY: 711894

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: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.77	T;T
M_CAP	Pathogenic	0.37	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-4.9	D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.82
MutPred		0.74		Gain of catalytic residue at L121 (P = 0.0018);Gain of catalytic residue at L121 (P = 0.0018);
MVP		0.71
MPC		1.7
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.95
gMVP		0.94

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.

Other links and lift over

hg19: chr14-50101494;