NM_017802.4:c.1257+13A>G

Variant names:

• chr7-754834-A-G
• rs34761279
• NM_017802.4:c.1257+13A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, PanelApp Australia
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 260922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017802.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF5	NM_017802.4	MANE Select	c.1257+13A>G		intron	N/A	NP_060272.3
	DNAAF5	NR_075098.2		n.1217+13A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF5	ENST00000297440.11	TSL:1 MANE Select	c.1257+13A>G		intron	N/A	ENSP00000297440.6
	DNAAF5	ENST00000852634.1		c.1338+13A>G		intron	N/A	ENSP00000522693.1
	DNAAF5	ENST00000852633.1		c.1257+13A>G		intron	N/A	ENSP00000522692.1

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

GnomAD2 exomes AF: 0.820 AC: 184047 AN: 224422 AF XY: 0.828

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 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

African (AFR) AF: 0.855 AC: 28114 AN: 32878

American (AMR) AF: 0.741 AC: 31191 AN: 42104

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 21529 AN: 25074

East Asian (EAS) AF: 0.725 AC: 28156 AN: 38810

South Asian (SAS) AF: 0.895 AC: 75271 AN: 84108

European-Finnish (FIN) AF: 0.799 AC: 41118 AN: 51476

Middle Eastern (MID) AF: 0.889 AC: 4544 AN: 5112

European-Non Finnish (NFE) AF: 0.836 AC: 908824 AN: 1087630

Other (OTH) AF: 0.832 AC: 48985 AN: 58878

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

African (AFR) AF: 0.846 AC: 35109 AN: 41520

American (AMR) AF: 0.824 AC: 12602 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2943 AN: 3472

East Asian (EAS) AF: 0.741 AC: 3809 AN: 5140

South Asian (SAS) AF: 0.898 AC: 4326 AN: 4818

European-Finnish (FIN) AF: 0.799 AC: 8456 AN: 10588

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56510 AN: 68010

Other (OTH) AF: 0.861 AC: 1821 AN: 2114

Alfa AF: 0.830 Hom.: 17238

Bravo AF: 0.833

Asia WGS AF: 0.840 AC: 2920 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)
-	-	1	Primary ciliary dyskinesia (1)
-	-	1	Primary ciliary dyskinesia 18 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.18
DANN	Benign	0.14
PhyloP100		-3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=11/89	disease causing

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

Other links and lift over

dbSNP: rs34761279; hg19: chr7-794471;