7-754809-C-A

Variant names:

• chr7-754809-C-A
• rs146922072
• NM_017802.4:c.1245C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_017802.4(DNAAF5):​c.1245C>A​(p.Ala415Ala) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A415A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAAF5 NM_017802.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14
• Publications: 0 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 (REVEL=0.203).
• BP7: Synonymous conserved (PhyloP=-3.14 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF5	NM_017802.4	c.1245C>A	p.Ala415Ala	synonymous_variant	Exon 5 of 13	ENST00000297440.11	NP_060272.3
DNAAF5	XM_024446813.2	c.1245C>A	p.Ala415Ala	synonymous_variant	Exon 5 of 12		XP_024302581.1
DNAAF5	NR_075098.2	n.1205C>A		non_coding_transcript_exon_variant	Exon 5 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF5	ENST00000297440.11	c.1245C>A	p.Ala415Ala	synonymous_variant	Exon 5 of 13	1	NM_017802.4	ENSP00000297440.6
DNAAF5	ENST00000440747.5	c.648C>A	p.Ala216Ala	synonymous_variant	Exon 5 of 13	2		ENSP00000403165.1
DNAAF5	ENST00000437419.5	c.561C>A	p.Ala187Ala	synonymous_variant	Exon 4 of 5	5		ENSP00000410788.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1451762 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 720522

African (AFR) AF: 0.00 AC: 0 AN: 33314

American (AMR) AF: 0.00 AC: 0 AN: 44292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25892

East Asian (EAS) AF: 0.00 AC: 0 AN: 39414

South Asian (SAS) AF: 0.00 AC: 0 AN: 85810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5622

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105212

Other (OTH) AF: 0.00 AC: 0 AN: 59930

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.18
DANN	Benign	0.62
PhyloP100		-3.1

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: rs146922072; hg19: chr7-794446;