rs763900107

Variant names:

• chr8-132610255-GA-G
• rs763900107
• NM_012472.6:c.1050delT

Your query was ambiguous. Multiple possible variants found:

• chr8-132610255-GA-G
• chr8-132610255-GA-GAA

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_012472.6(DNAAF11):​c.1050delT​(p.Gln351SerfsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAAF11 NM_012472.6 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.13
• 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, G2P, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Pathogenic. The variant received 12 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
• PP5: Variant 8-132610255-GA-G is Pathogenic according to our data. Variant chr8-132610255-GA-G is described in ClinVar as Pathogenic. ClinVar VariationId is 540328.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1050delT	p.Gln351SerfsTer8	frameshift	Exon 10 of 12	NP_036604.2
	DNAAF11	NM_001321961.2		c.990delT	p.Gln331SerfsTer8	frameshift	Exon 9 of 11	NP_001308890.1
	DNAAF11	NM_001321962.2		c.804delT	p.Gln269SerfsTer8	frameshift	Exon 8 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.1050delT	p.Gln351SerfsTer8	frameshift	Exon 10 of 12	ENSP00000484634.1	Q86X45-1
	DNAAF11	ENST00000519595.5	TSL:1	c.1050delT	p.Gln351SerfsTer8	frameshift	Exon 10 of 12	ENSP00000429791.1	Q86X45-1
	DNAAF11	ENST00000250173.5	TSL:1	c.1045-4delT		splice_region intron	N/A	ENSP00000250173.2	G5EA20

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Primary ciliary dyskinesia 19 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=0/200	disease causing (ClinVar)

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: rs763900107; hg19: chr8-133622501;