17-11598497-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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 (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (170 hom.)
• Consequence: DNAH9 NM_001372.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.147

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]

ACMG classification

Verdict is Benign. Variant got -14 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 criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
DNAH9	NM_001372.4	c.-2C>T		5_prime_UTR_variant	1/69	ENST00000262442.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH9	ENST00000262442.9	c.-2C>T		5_prime_UTR_variant	1/69	1	NM_001372.4	P1
DNAH9	ENST00000579406.1	n.26C>T		non_coding_transcript_exon_variant	1/8	1
DNAH9	ENST00000579828.5	c.-2C>T		5_prime_UTR_variant	1/4	2
DNAH9	ENST00000454412.6			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.00406 AC: 617 AN: 152150 Hom.: 23 Cov.: 32

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: 87 AN: 4784 Hom.: 5 AF XY: 0.0174 AC XY: 47 AN XY: 2696

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.: 33 AF XY: 0.00346 AC XY: 2038 AN XY: 589494

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.: 23 Cov.: 32 AF XY: 0.00430 AC XY: 320 AN XY: 74450

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.: 0

Bravo AF: 0.00398

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

DNAH9-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 18, 2019

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

Other links and lift over

dbSNP: rs12604013; hg19: chr17-11501814;