Genetic Variant DNAH9:c.-2C>T (chr17-11598497-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001372.4(DNAH9):c.-2C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,366,578 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0041 ( 23 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 170 hom. )

Consequence

DNAH9
NM_001372.4 5_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.147

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 17-11598497-C-T is Benign according to our data. Variant chr17-11598497-C-T is described in ClinVar as [Benign]. Clinvar id is 3044413.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH9	NM_001372.4 link	c.-2C>T		5_prime_UTR_variant	Exon 1 of 69	ENST00000262442.9	NP_001363.2	Q9NYC9-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH9	ENST00000262442 link	c.-2C>T	5_prime_UTR_variant	Exon 1 of 69	1	NM_001372.4	ENSP00000262442.3	Q9NYC9-1
DNAH9	ENST00000579406.1 link	n.26C>T	non_coding_transcript_exon_variant	Exon 1 of 8	1
DNAH9	ENST00000579828 link	c.-2C>T	5_prime_UTR_variant	Exon 1 of 4	2		ENSP00000463782.1	J3QQK8
DNAH9	ENST00000454412.6 link	c.-2C>T	upstream_gene_variant		5		ENSP00000414874.2	E7EP17

Frequencies

GnomAD3 genomes

AF:

0.00406

AC:

617

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0811

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.0182

AC:

AN:

4784

Hom.:

AF XY:

0.0174

AC XY:

AN XY:

2696

show subpopulations

Gnomad AFR exome

AF:

0.00360

Gnomad AMR exome

AF:

0.00112

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.149

Gnomad SAS exome

AF:

0.0390

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000491

Gnomad OTH exome

AF:

0.00833

GnomAD4 exome

AF:

0.00326

AC:

3954

AN:

1214310

Hom.:

170

Cov.:

AF XY:

0.00346

AC XY:

2038

AN XY:

589494

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000989

Gnomad4 ASJ exome

AF:

0.000412

Gnomad4 EAS exome

AF:

0.0918

Gnomad4 SAS exome

AF:

0.0157

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000999

Gnomad4 OTH exome

AF:

0.00969

GnomAD4 genome

AF:

0.00407

AC:

619

AN:

152268

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

320

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000649

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0813

Gnomad4 SAS

AF:

0.0209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.0000696

Hom.:

Bravo

AF:

0.00398

Asia WGS

AF:

0.0430

AC:

150

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DNAH9-related disorder

Benign:1

Jun 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.3

DANN

Benign

0.88

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over