rs543710960

Variant names:

• chr7-729778-T-C
• rs543710960
• NM_017802.4:c.711T>C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4 BP6_Very_Strong BP7 BS1 BS2

The NM_017802.4(DNAAF5):​c.711T>C​(p.Phe237Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000313 in 1,614,252 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (2 hom.)
• Consequence: DNAAF5 NM_017802.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.235
• 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.269).
• BP6: Variant 7-729778-T-C is Benign according to our data. Variant chr7-729778-T-C is described in ClinVar as Benign. ClinVar VariationId is 241210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.235 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00155 (236/152374) while in subpopulation AFR AF = 0.00529 (220/41594). AF 95% confidence interval is 0.00472. There are 1 homozygotes in GnomAd4. There are 124 alleles in the male GnomAd4 subpopulation. Median coverage is 32. 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.711T>C	p.Phe237Phe	synonymous	Exon 2 of 13	NP_060272.3
	DNAAF5	NR_075098.2		n.671T>C		non_coding_transcript_exon	Exon 2 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF5	ENST00000297440.11	TSL:1 MANE Select	c.711T>C	p.Phe237Phe	synonymous	Exon 2 of 13	ENSP00000297440.6	Q86Y56-1
	DNAAF5	ENST00000852634.1		c.711T>C	p.Phe237Phe	synonymous	Exon 2 of 14	ENSP00000522693.1
	DNAAF5	ENST00000852633.1		c.711T>C	p.Phe237Phe	synonymous	Exon 2 of 13	ENSP00000522692.1

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 235 AN: 152256 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00528

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000414 AC: 104 AN: 251150 AF XY: 0.000339

Gnomad AFR exome AF: 0.00573

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000184 AC: 269 AN: 1461878 Hom.: 2 Cov.: 31 AF XY: 0.000162 AC XY: 118 AN XY: 727240

African (AFR) AF: 0.00606 AC: 203 AN: 33480

American (AMR) AF: 0.000157 AC: 7 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53416

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1112006

Other (OTH) AF: 0.000447 AC: 27 AN: 60394

GnomAD4 genome AF: 0.00155 AC: 236 AN: 152374 Hom.: 1 Cov.: 32 AF XY: 0.00166 AC XY: 124 AN XY: 74508

African (AFR) AF: 0.00529 AC: 220 AN: 41594

American (AMR) AF: 0.000392 AC: 6 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68038

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.00158

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.4
DANN	Benign	0.40
PhyloP100		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=99/1	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: rs543710960; hg19: chr7-769415;