NM_017802.4:c.2082+8delG

Variant names:

• chr7-774202-CG-C
• rs878855035
• NM_017802.4:c.2082+8delG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_017802.4(DNAAF5):​c.2082+8delG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000323 in 1,602,146 control chromosomes in the GnomAD database, including 2 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00018 (2 hom.)
• Consequence: DNAAF5 NM_017802.4 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.698
• Publications: 1 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 -16 ACMG points.

• BP6: Variant 7-774202-CG-C is Benign according to our data. Variant chr7-774202-CG-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241201.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 = 0.00172 (262/152282) while in subpopulation AFR AF = 0.00578 (240/41542). AF 95% confidence interval is 0.00518. There are 0 homozygotes in GnomAd4. There are 116 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 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.2082+8delG		splice_region intron	N/A	NP_060272.3
	DNAAF5	NR_075098.2		n.2042+8delG		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF5	ENST00000297440.11	TSL:1 MANE Select	c.2082+5delG		splice_region intron	N/A	ENSP00000297440.6	Q86Y56-1
	DNAAF5	ENST00000403952.3	TSL:1	c.357+5delG		splice_region intron	N/A	ENSP00000384884.3	E9PGY2
	DNAAF5	ENST00000852634.1		c.2163+5delG		splice_region intron	N/A	ENSP00000522693.1

Frequencies

GnomAD3 genomes AF: 0.00170 AC: 258 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00570

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

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: 0.00

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000373 AC: 88 AN: 235990 AF XY: 0.000280

Gnomad AFR exome AF: 0.00501

Gnomad AMR exome AF: 0.000235

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000340

GnomAD4 exome AF: 0.000177 AC: 256 AN: 1449864 Hom.: 2 Cov.: 38 AF XY: 0.000164 AC XY: 118 AN XY: 721242

African (AFR) AF: 0.00608 AC: 203 AN: 33398

American (AMR) AF: 0.000406 AC: 18 AN: 44346

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25742

East Asian (EAS) AF: 0.00 AC: 0 AN: 39604

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45996

Middle Eastern (MID) AF: 0.000698 AC: 4 AN: 5732

European-Non Finnish (NFE) AF: 0.00000541 AC: 6 AN: 1109120

Other (OTH) AF: 0.000399 AC: 24 AN: 60128

GnomAD4 genome AF: 0.00172 AC: 262 AN: 152282 Hom.: 0 Cov.: 33 AF XY: 0.00156 AC XY: 116 AN XY: 74462

African (AFR) AF: 0.00578 AC: 240 AN: 41542

American (AMR) AF: 0.00124 AC: 19 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000999 Hom.: 0

Bravo AF: 0.00194

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.70
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: rs878855035; hg19: chr7-813839;