17-11854239-C-G

Variant names:

• chr17-11854239-C-G
• rs12449553
• NM_001372.4:c.9744C>G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001372.4(DNAH9):​c.9744C>G​(p.Pro3248Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 1,613,906 control chromosomes in the GnomAD database, including 141,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12611 hom., cov: 32)
  • Exomes 𝑓: 0.42 (128397 hom.)
• Consequence: DNAH9 NM_001372.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -4.91

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=-0.89).
• BP6: Variant 17-11854239-C-G is Benign according to our data. Variant chr17-11854239-C-G is described in ClinVar as [Benign]. Clinvar id is 402782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH9	NM_001372.4	c.9744C>G	p.Pro3248Pro	synonymous_variant	Exon 50 of 69	ENST00000262442.9	NP_001363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH9	ENST00000262442.9	c.9744C>G	p.Pro3248Pro	synonymous_variant	Exon 50 of 69	1	NM_001372.4	ENSP00000262442.3
DNAH9	ENST00000454412.6	c.9744C>G	p.Pro3248Pro	synonymous_variant	Exon 50 of 68	5		ENSP00000414874.2
DNAH9	ENST00000579703.1	c.186C>G	p.Pro62Pro	synonymous_variant	Exon 1 of 4	3		ENSP00000463622.2
DNAH9	ENST00000578834.1	n.291C>G		non_coding_transcript_exon_variant	Exon 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60887 AN: 151906 Hom.: 12601 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.417

GnomAD3 exomes AF: 0.432 AC: 108654 AN: 251438 Hom.: 24829 AF XY: 0.424 AC XY: 57571 AN XY: 135898

Gnomad AFR exome AF: 0.324

Gnomad AMR exome AF: 0.663

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.378

Gnomad SAS exome AF: 0.408

Gnomad FIN exome AF: 0.406

Gnomad NFE exome AF: 0.405

Gnomad OTH exome AF: 0.434

GnomAD4 exome AF: 0.416 AC: 607421 AN: 1461882 Hom.: 128397 Cov.: 71 AF XY: 0.413 AC XY: 300160 AN XY: 727246

Gnomad4 AFR exome AF: 0.322

Gnomad4 AMR exome AF: 0.649

Gnomad4 ASJ exome AF: 0.353

Gnomad4 EAS exome AF: 0.356

Gnomad4 SAS exome AF: 0.402

Gnomad4 FIN exome AF: 0.402

Gnomad4 NFE exome AF: 0.415

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.401 AC: 60921 AN: 152024 Hom.: 12611 Cov.: 32 AF XY: 0.400 AC XY: 29734 AN XY: 74338

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.415

Alfa AF: 0.319 Hom.: 1327

Bravo AF: 0.409

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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: Frequency -

Ciliary dyskinesia, primary, 40 Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.043
DANN	Benign	0.47

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: rs12449553; hg19: chr17-11757556; COSMIC: COSV52335004;