7-775151-G-C

Variant names:

• chr7-775151-G-C
• rs3922641
• NM_017802.4:c.2228G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017802.4(DNAAF5):​c.2228G>C​(p.Arg743Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R743K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAAF5 NM_017802.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.716
• Publications: 40 publications found

Genes affected

DNAAF5 (HGNC:26013): (dynein axonemal assembly factor 5) The protein encoded by this gene is essential for the preassembly or stability of axonemal dynein arms, and is found only in organisms with motile cilia and flagella. Mutations in this gene are associated with primary ciliary dyskinesia-18, a disorder characterized by abnormalities of motile cilia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]

DNAAF5 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 18

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11180258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF5	NM_017802.4	c.2228G>C	p.Arg743Thr	missense_variant	Exon 11 of 13	ENST00000297440.11	NP_060272.3
DNAAF5	XM_024446813.2	c.2228G>C	p.Arg743Thr	missense_variant	Exon 11 of 12		XP_024302581.1
DNAAF5	NR_075098.2	n.2188G>C		non_coding_transcript_exon_variant	Exon 11 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF5	ENST00000297440.11	c.2228G>C	p.Arg743Thr	missense_variant	Exon 11 of 13	1	NM_017802.4	ENSP00000297440.6
DNAAF5	ENST00000403952.3	c.503G>C	p.Arg168Thr	missense_variant	Exon 4 of 6	1		ENSP00000384884.3
DNAAF5	ENST00000440747.5	c.1631G>C	p.Arg544Thr	missense_variant	Exon 11 of 13	2		ENSP00000403165.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 83514

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.25	T;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.39	T;T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.91	T
PhyloP100		0.72
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.050	B;B
Vest4		0.11
MutPred		0.47		Loss of helix (P = 0.0237);.;
MVP		0.085
MPC		0.25
ClinPred		0.77	D
GERP RS		2.8
Varity_R		0.14
gMVP		0.12
Mutation Taster		=83/17	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: rs3922641; hg19: chr7-814788;