rs114907681

Variant names:

• chr7-785557-G-A
• rs114907681
• NM_017802.4:c.2472G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_017802.4(DNAAF5):​c.2472G>A​(p.Leu824Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000592 in 1,613,612 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00033 (3 hom.)
• Consequence: DNAAF5 NM_017802.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.316

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 7-785557-G-A is Benign according to our data. Variant chr7-785557-G-A is described in ClinVar as [Benign]. Clinvar id is 454861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.316 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00306 (467/152366) while in subpopulation AFR AF= 0.0104 (434/41588). AF 95% confidence interval is 0.00963. There are 2 homozygotes in gnomad4. There are 226 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF5	NM_017802.4	c.2472G>A	p.Leu824Leu	synonymous_variant	Exon 13 of 13	ENST00000297440.11	NP_060272.3
DNAAF5	XM_024446813.2	c.2280G>A	p.Leu760Leu	synonymous_variant	Exon 12 of 12		XP_024302581.1
DNAAF5	NR_075098.2	n.2432G>A		non_coding_transcript_exon_variant	Exon 13 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF5	ENST00000297440.11	c.2472G>A	p.Leu824Leu	synonymous_variant	Exon 13 of 13	1	NM_017802.4	ENSP00000297440.6
DNAAF5	ENST00000403952.3	c.747G>A	p.Leu249Leu	synonymous_variant	Exon 6 of 6	1		ENSP00000384884.3
DNAAF5	ENST00000440747.5	c.1875G>A	p.Leu625Leu	synonymous_variant	Exon 13 of 13	2		ENSP00000403165.1
DNAAF5	ENST00000461576.1	n.282G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.00306 AC: 466 AN: 152248 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.000749 AC: 188 AN: 250914 Hom.: 2 AF XY: 0.000545 AC XY: 74 AN XY: 135740

Gnomad AFR exome AF: 0.0102

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000334 AC: 488 AN: 1461246 Hom.: 3 Cov.: 33 AF XY: 0.000290 AC XY: 211 AN XY: 726950

Gnomad4 AFR exome AF: 0.0109

Gnomad4 AMR exome AF: 0.000648

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.00106

GnomAD4 genome AF: 0.00306 AC: 467 AN: 152366 Hom.: 2 Cov.: 33 AF XY: 0.00303 AC XY: 226 AN XY: 74516

Gnomad4 AFR AF: 0.0104

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00187 Hom.: 3

Bravo AF: 0.00365

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Dec 17, 2019

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Mar 01, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.6
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs114907681; hg19: chr7-825194;