rs2286303

chr17-11929970-A-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.11982A>G(p.Pro3994=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,613,536 control chromosomes in the GnomAD database, including 77,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5576 hom., cov: 31)
  • Exomes 𝑓: 0.31 (72026 hom.)
• Consequence: DNAH9 NM_001372.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.51

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=-0.79).
• BP6: Variant 17-11929970-A-G is Benign according to our data. Variant chr17-11929970-A-G is described in ClinVar as [Benign]. Clinvar id is 402784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH9	NM_001372.4	c.11982A>G	p.Pro3994=	synonymous_variant	63/69	ENST00000262442.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH9	ENST00000262442.9	c.11982A>G	p.Pro3994=	synonymous_variant	63/69	1	NM_001372.4	P1
DNAH9	ENST00000608377.5	c.918A>G	p.Pro306=	synonymous_variant	9/15	1
DNAH9	ENST00000396001.6	n.1445A>G		non_coding_transcript_exon_variant	9/15	1
DNAH9	ENST00000454412.6	c.11878-2044A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38808 AN: 151868 Hom.: 5574 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.292

GnomAD3 exomes AF: 0.285 AC: 71526 AN: 250620 Hom.: 10949 AF XY: 0.294 AC XY: 39843 AN XY: 135452

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.200

Gnomad ASJ exome AF: 0.360

Gnomad EAS exome AF: 0.203

Gnomad SAS exome AF: 0.305

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.331

Gnomad OTH exome AF: 0.318

GnomAD4 exome AF: 0.310 AC: 452413 AN: 1461548 Hom.: 72026 Cov.: 37 AF XY: 0.312 AC XY: 226953 AN XY: 727034

Gnomad4 AFR exome AF: 0.0971

Gnomad4 AMR exome AF: 0.209

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.324

Gnomad4 OTH exome AF: 0.302

GnomAD4 genome AF: 0.255 AC: 38810 AN: 151988 Hom.: 5576 Cov.: 31 AF XY: 0.256 AC XY: 19004 AN XY: 74278

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.291

Alfa AF: 0.313 Hom.: 9820

Bravo AF: 0.240

Asia WGS AF: 0.238 AC: 826 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

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: MAF -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.14
Dann	Benign	0.65

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: rs2286303; hg19: chr17-11833287; COSMIC: COSV52351486; COSMIC: COSV52351486;