chr7-741478-G-T

Variant names:

• chr7-741478-G-T
• rs773831457
• NM_017802.4:c.1024+13G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017802.4(DNAAF5):​c.1024+13G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000087 in 1,149,820 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: DNAAF5 NM_017802.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF5	NM_017802.4	c.1024+13G>T		intron_variant	Intron 4 of 12	ENST00000297440.11	NP_060272.3
DNAAF5	NR_075098.2	n.984+13G>T		intron_variant	Intron 4 of 12
DNAAF5	XM_024446813.2	c.1024+13G>T		intron_variant	Intron 4 of 11		XP_024302581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF5	ENST00000297440.11	c.1024+13G>T		intron_variant	Intron 4 of 12	1	NM_017802.4	ENSP00000297440.6
DNAAF5	ENST00000440747.5	c.427+13G>T		intron_variant	Intron 4 of 12	2		ENSP00000403165.1
DNAAF5	ENST00000437419.5	c.340+13G>T		intron_variant	Intron 3 of 4	5		ENSP00000410788.1
DNAAF5	ENST00000438961.1	n.493+13G>T		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.70e-7 AC: 1 AN: 1149820 Hom.: 0 Cov.: 20 AF XY: 0.00000176 AC XY: 1 AN XY: 569564

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000383 AC: 1 AN: 26136

American (AMR) AF: 0.00 AC: 0 AN: 31288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18066

East Asian (EAS) AF: 0.00 AC: 0 AN: 22698

South Asian (SAS) AF: 0.00 AC: 0 AN: 76456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3574

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 891828

Other (OTH) AF: 0.00 AC: 0 AN: 43926

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.29
DANN	Benign	0.36
PhyloP100		-0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs773831457; hg19: chr7-781115;