rs193920997

Variant names:

• chr17-11669625-A-G
• rs193920997
• NM_001372.4:c.3184A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001372.4(DNAH9):​c.3184A>G​(p.Ile1062Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. I1062I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH9 NM_001372.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.27
• Publications: 0 publications found

Genes affected

DNAH9 (HGNC:2953): (dynein axonemal heavy chain 9) This gene encodes the heavy chain subunit of axonemal dynein, a large multi-subunit molecular motor. Axonemal dynein attaches to microtubules and hydrolyzes ATP to mediate the movement of cilia and flagella. The gene expresses at least two transcript variants; additional variants have been described, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

DNAH9 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 40

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• schizophrenia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19264537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH9	NM_001372.4	c.3184A>G	p.Ile1062Val	missense_variant	Exon 17 of 69	ENST00000262442.9	NP_001363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH9	ENST00000262442.9	c.3184A>G	p.Ile1062Val	missense_variant	Exon 17 of 69	1	NM_001372.4	ENSP00000262442.3
DNAH9	ENST00000454412.6	c.3184A>G	p.Ile1062Val	missense_variant	Exon 17 of 68	5		ENSP00000414874.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

-

Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.099
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;.
PhyloP100		3.3
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.65	N;N
REVEL	Benign	0.053
Sift	Benign	0.053	T;D
Polyphen		0.017	B;.
Vest4		0.16
MutPred		0.43		Gain of ubiquitination at K1059 (P = 0.1079);Gain of ubiquitination at K1059 (P = 0.1079);
MVP		0.57
MPC		0.11
ClinPred		0.64	D
GERP RS		4.8
Varity_R		0.089
gMVP		0.12
Mutation Taster		=97/3	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: rs193920997; hg19: chr17-11572942; COSMIC: COSV52340603;