chrX-107222767-CAGGTGGG-C

Variant names:

• chrX-107222767-CAGGTGGG-C
• rs1057519568
• NM_173494.2:c.357_363delGGTGGGA

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_173494.2(DNAAF6):​c.357_363delGGTGGGA​(p.Val120LeufsTer6) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 22)
• Consequence: DNAAF6 NM_173494.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.24
• Publications: 1 publications found

Genes affected

DNAAF6 (HGNC:28570): (dynein axonemal assembly factor 6) Enables dynein intermediate chain binding activity. Involved in flagellated sperm motility; inner dynein arm assembly; and outer dynein arm assembly. Located in trans-Golgi network. Implicated in primary ciliary dyskinesia 36. [provided by Alliance of Genome Resources, Apr 2022]

DNAAF6 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 36, X-linked

  Inheritance: XL Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 11 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 X-107222767-CAGGTGGG-C is Pathogenic according to our data. Variant chrX-107222767-CAGGTGGG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 375562.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF6	NM_173494.2	c.357_363delGGTGGGA	p.Val120LeufsTer6	frameshift_variant	Exon 5 of 7	ENST00000372453.8	NP_775765.1
DNAAF6	NM_001169154.2	c.357_363delGGTGGGA	p.Val120LeufsTer6	frameshift_variant	Exon 6 of 8		NP_001162625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF6	ENST00000372453.8	c.357_363delGGTGGGA	p.Val120LeufsTer6	frameshift_variant	Exon 5 of 7	1	NM_173494.2	ENSP00000361531.3
DNAAF6	ENST00000336387.4	c.357_363delGGTGGGA	p.Val120LeufsTer6	frameshift_variant	Exon 5 of 7	5		ENSP00000337757.4
DNAAF6	ENST00000535523.6	c.357_363delGGTGGGA	p.Val120LeufsTer6	frameshift_variant	Exon 6 of 8	5		ENSP00000441930.1
DNAAF6	ENST00000688816.1	c.332+3800_332+3806delGGTGGGA		intron_variant	Intron 4 of 5			ENSP00000508655.1

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Ciliary dyskinesia, primary, 36, X-linked Pathogenic:1

Feb 08, 2017

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.2
Mutation Taster		=0/200	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs1057519568; hg19: chrX-106465997;