rs34761279

chr7-754834-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017802.4(DNAAF5):c.1257+13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 1,578,238 control chromosomes in the GnomAD database, including 548,324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52691 hom., cov: 33)
  • Exomes 𝑓: 0.83 (495633 hom.)
• Consequence: DNAAF5 NM_017802.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.79

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 7-754834-A-G is Benign according to our data. Variant chr7-754834-A-G is described in ClinVar as [Benign]. Clinvar id is 260922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-754834-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAAF5	NM_017802.4	c.1257+13A>G		intron_variant		ENST00000297440.11
DNAAF5	XM_024446813.2	c.1257+13A>G		intron_variant
DNAAF5	NR_075098.2	n.1217+13A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF5	ENST00000297440.11	c.1257+13A>G		intron_variant		1	NM_017802.4	P1
DNAAF5	ENST00000437419.5	c.574+13A>G		intron_variant		5
DNAAF5	ENST00000440747.5	c.661+13A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126419 AN: 152050 Hom.: 52638 Cov.: 33

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.859

GnomAD3 exomes AF: 0.820 AC: 184047 AN: 224422 Hom.: 75736 AF XY: 0.828 AC XY: 101369 AN XY: 122480

Gnomad AFR exome AF: 0.847

Gnomad AMR exome AF: 0.728

Gnomad ASJ exome AF: 0.862

Gnomad EAS exome AF: 0.762

Gnomad SAS exome AF: 0.894

Gnomad FIN exome AF: 0.797

Gnomad NFE exome AF: 0.835

Gnomad OTH exome AF: 0.838

GnomAD4 exome AF: 0.833 AC: 1187732 AN: 1426070 Hom.: 495633 Cov.: 27 AF XY: 0.835 AC XY: 589432 AN XY: 705930

Gnomad4 AFR exome AF: 0.855

Gnomad4 AMR exome AF: 0.741

Gnomad4 ASJ exome AF: 0.859

Gnomad4 EAS exome AF: 0.725

Gnomad4 SAS exome AF: 0.895

Gnomad4 FIN exome AF: 0.799

Gnomad4 NFE exome AF: 0.836

Gnomad4 OTH exome AF: 0.832

GnomAD4 genome AF: 0.831 AC: 126526 AN: 152168 Hom.: 52691 Cov.: 33 AF XY: 0.831 AC XY: 61823 AN XY: 74402

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.824

Gnomad4 ASJ AF: 0.848

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.898

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.861

Alfa AF: 0.830 Hom.: 9720

Bravo AF: 0.833

Asia WGS AF: 0.840 AC: 2920 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Primary ciliary dyskinesia 18 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.18
Dann	Benign	0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34761279; hg19: chr7-794471;