7-741476-G-T

Variant names:

• chr7-741476-G-T
• rs201554395
• NM_017802.4:c.1024+11G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_017802.4(DNAAF5):​c.1024+11G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,226,746 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0070 (13 hom., cov: 32)
  • Exomes 𝑓: 0.00079 (6 hom.)
• Consequence: DNAAF5 NM_017802.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0220
• 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: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
• 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=-0.86).
• BP6: Variant 7-741476-G-T is Benign according to our data. Variant chr7-741476-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00696 (970/139326) while in subpopulation AFR AF = 0.024 (931/38816). AF 95% confidence interval is 0.0227. There are 13 homozygotes in GnomAd4. There are 478 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR,AD gene

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.1024+11G>T		intron	N/A	NP_060272.3
	DNAAF5	NR_075098.2		n.984+11G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF5	ENST00000297440.11	TSL:1 MANE Select	c.1024+11G>T		intron	N/A	ENSP00000297440.6	Q86Y56-1
	DNAAF5	ENST00000852634.1		c.1105+11G>T		intron	N/A	ENSP00000522693.1
	DNAAF5	ENST00000852633.1		c.1024+11G>T		intron	N/A	ENSP00000522692.1

Frequencies

GnomAD3 genomes AF: 0.00696 AC: 969 AN: 139236 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0240

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00187

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.0000624

Gnomad OTH AF: 0.00413

GnomAD2 exomes AF: 0.00149 AC: 262 AN: 175406 AF XY: 0.00110

Gnomad AFR exome AF: 0.0217

Gnomad AMR exome AF: 0.000865

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000139

Gnomad OTH exome AF: 0.000426

GnomAD4 exome AF: 0.000792 AC: 861 AN: 1087420 Hom.: 6 Cov.: 20 AF XY: 0.000699 AC XY: 376 AN XY: 537844

African (AFR) AF: 0.0289 AC: 716 AN: 24774

American (AMR) AF: 0.00124 AC: 37 AN: 29784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16112

East Asian (EAS) AF: 0.00 AC: 0 AN: 17040

South Asian (SAS) AF: 0.0000264 AC: 2 AN: 75646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32152

Middle Eastern (MID) AF: 0.000909 AC: 3 AN: 3302

European-Non Finnish (NFE) AF: 0.0000495 AC: 42 AN: 848250

Other (OTH) AF: 0.00151 AC: 61 AN: 40360

GnomAD4 genome AF: 0.00696 AC: 970 AN: 139326 Hom.: 13 Cov.: 32 AF XY: 0.00709 AC XY: 478 AN XY: 67396

African (AFR) AF: 0.0240 AC: 931 AN: 38816

American (AMR) AF: 0.00187 AC: 26 AN: 13914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3292

East Asian (EAS) AF: 0.00 AC: 0 AN: 3914

South Asian (SAS) AF: 0.00 AC: 0 AN: 3812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8410

Middle Eastern (MID) AF: 0.00350 AC: 1 AN: 286

European-Non Finnish (NFE) AF: 0.0000624 AC: 4 AN: 64064

Other (OTH) AF: 0.00408 AC: 8 AN: 1960

Alfa AF: 0.000504 Hom.: 0

Bravo AF: 0.00701

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.51
DANN	Benign	0.44
PhyloP100		0.022
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs201554395; hg19: chr7-781113;