Variant chr17-11598568-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_001372.4(DNAH9):c.70C>T(p.Arg24Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000835 in 1,197,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 8.4e-7 ( 0 hom. )

Consequence

DNAH9
NM_001372.4 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 0.244

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 8 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 17-11598568-C-T is Pathogenic according to our data. Variant chr17-11598568-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2782150.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH9	NM_001372.4 linkuse as main transcript	c.70C>T	p.Arg24Ter	stop_gained	1/69	ENST00000262442.9	NP_001363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH9	ENST00000262442.9 linkuse as main transcript	c.70C>T	p.Arg24Ter	stop_gained	1/69	1	NM_001372.4	ENSP00000262442	P1	Q9NYC9-1
DNAH9	ENST00000579406.1 linkuse as main transcript	n.97C>T		non_coding_transcript_exon_variant	1/8	1
DNAH9	ENST00000454412.6 linkuse as main transcript	c.70C>T	p.Arg24Ter	stop_gained	1/68	5		ENSP00000414874
DNAH9	ENST00000579828.5 linkuse as main transcript	c.70C>T	p.Arg24Ter	stop_gained	1/4	2		ENSP00000463782

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.35e-7

AC:

AN:

1197330

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

585708

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000103

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 27, 2023

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with DNAH9-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg24*) in the DNAH9 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAH9 are known to be pathogenic (PMID: 30471718). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Benign

0.12

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.28

MutationTaster

Benign

1.0

A;A;A

Vest4

0.077

GERP RS

-2.0

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over