rs117483481

chr17-11854038-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001372.4(DNAH9):c.9543G>A(p.Pro3181=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00415 in 1,614,032 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0042 (45 hom.)
• Consequence: DNAH9 NM_001372.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -5.31

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 17-11854038-G-A is Benign according to our data. Variant chr17-11854038-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 402781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.31 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00368 (560/152192) while in subpopulation EAS AF= 0.0321 (166/5170). AF 95% confidence interval is 0.0281. There are 3 homozygotes in gnomad4. There are 263 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH9	NM_001372.4	c.9543G>A	p.Pro3181=	synonymous_variant	50/69	ENST00000262442.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH9	ENST00000262442.9	c.9543G>A	p.Pro3181=	synonymous_variant	50/69	1	NM_001372.4	P1
DNAH9	ENST00000454412.6	c.9543G>A	p.Pro3181=	synonymous_variant	50/68	5
DNAH9	ENST00000578834.1	n.90G>A		non_coding_transcript_exon_variant	2/3	4
DNAH9	ENST00000579703.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00369 AC: 561 AN: 152074 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.0320

Gnomad SAS AF: 0.00644

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00362

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00589 AC: 1479 AN: 251242 Hom.: 20 AF XY: 0.00585 AC XY: 794 AN XY: 135816

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.0124

Gnomad EAS exome AF: 0.0370

Gnomad SAS exome AF: 0.00536

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.00356

Gnomad OTH exome AF: 0.00473

GnomAD4 exome AF: 0.00420 AC: 6139 AN: 1461840 Hom.: 45 Cov.: 30 AF XY: 0.00427 AC XY: 3103 AN XY: 727220

Gnomad4 AFR exome AF: 0.000896

Gnomad4 AMR exome AF: 0.00174

Gnomad4 ASJ exome AF: 0.0108

Gnomad4 EAS exome AF: 0.0225

Gnomad4 SAS exome AF: 0.00589

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.00352

Gnomad4 OTH exome AF: 0.00604

GnomAD4 genome AF: 0.00368 AC: 560 AN: 152192 Hom.: 3 Cov.: 31 AF XY: 0.00353 AC XY: 263 AN XY: 74404

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.00223

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.0321

Gnomad4 SAS AF: 0.00624

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00362

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00376 Hom.: 3

Bravo AF: 0.00365

Asia WGS AF: 0.00837 AC: 29 AN: 3478

EpiCase AF: 0.00376

EpiControl AF: 0.00462

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Candidate PCD gene, but frequency is high -

DNAH9-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 27, 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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Ciliary dyskinesia, primary, 40 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Nov 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.18
Dann	Benign	0.81

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: rs117483481; hg19: chr17-11757355; COSMIC: COSV52361175; COSMIC: COSV52361175;