NM_012472.6:c.633C>G

Variant names:

• chr8-132632760-G-C
• NM_012472.6:c.633C>G
• DNAAF11 p.Tyr211*

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_012472.6(DNAAF11):​c.633C>G​(p.Tyr211*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Y211Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAAF11 NM_012472.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.731
• Publications: 0 publications found

Genes affected

DNAAF11 (HGNC:16725): (dynein axonemal assembly factor 11) The protein encoded by this gene contains several leucine-rich repeat domains and appears to be involved in the motility of cilia. Defects in this gene are a cause of primary ciliary dyskinesia-19 (CILD19). Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 4, 11 and 22. [provided by RefSeq, Apr 2016]

DNAAF11 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 19

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012472.6. 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
	DNAAF11	NM_012472.6	MANE Select	c.633C>G	p.Tyr211*	stop_gained	Exon 5 of 12	NP_036604.2
	DNAAF11	NM_001321961.2		c.633C>G	p.Tyr211*	stop_gained	Exon 5 of 11	NP_001308890.1
	DNAAF11	NM_001321962.2		c.387C>G	p.Tyr129*	stop_gained	Exon 3 of 10	NP_001308891.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF11	ENST00000620350.5	TSL:1 MANE Select	c.633C>G	p.Tyr211*	stop_gained	Exon 5 of 12	ENSP00000484634.1	Q86X45-1
	DNAAF11	ENST00000519595.5	TSL:1	c.633C>G	p.Tyr211*	stop_gained	Exon 5 of 12	ENSP00000429791.1	Q86X45-1
	DNAAF11	ENST00000250173.5	TSL:1	c.633C>G	p.Tyr211*	stop_gained	Exon 5 of 13	ENSP00000250173.2	G5EA20

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	33
DANN	Uncertain	1.0
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.027
FATHMM_MKL	Benign	0.55	D
PhyloP100		0.73
Mutation Taster		=2/198	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-133645006;