rs8070256

Positions:

• chr17-11883634-T-C

Variant summary

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

The ENST00000262442.9(DNAH9):​c.10855T>C​(p.Leu3619=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,613,760 control chromosomes in the GnomAD database, including 185,136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (13350 hom., cov: 32)
  • Exomes 𝑓: 0.48 (171786 hom.)
• Consequence: DNAH9 ENST00000262442.9 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.502

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=-0.86).
• BP6: Variant 17-11883634-T-C is Benign according to our data. Variant chr17-11883634-T-C is described in ClinVar as [Benign]. Clinvar id is 402783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.502 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH9	NM_001372.4	c.10855T>C	p.Leu3619=	synonymous_variant	56/69	ENST00000262442.9	NP_001363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH9	ENST00000262442.9	c.10855T>C	p.Leu3619=	synonymous_variant	56/69	1	NM_001372.4	ENSP00000262442	P1
DNAH9	ENST00000608377.5	c.-210T>C		5_prime_UTR_variant	2/15	1		ENSP00000476951
DNAH9	ENST00000396001.6	n.318T>C		non_coding_transcript_exon_variant	2/15	1
DNAH9	ENST00000454412.6	c.10855T>C	p.Leu3619=	synonymous_variant	56/68	5		ENSP00000414874

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60390 AN: 151892 Hom.: 13357 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.464

GnomAD3 exomes AF: 0.448 AC: 112695 AN: 251360 Hom.: 26973 AF XY: 0.463 AC XY: 62912 AN XY: 135830

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.527

Gnomad EAS exome AF: 0.490

Gnomad SAS exome AF: 0.503

Gnomad FIN exome AF: 0.458

Gnomad NFE exome AF: 0.504

Gnomad OTH exome AF: 0.485

GnomAD4 exome AF: 0.480 AC: 701922 AN: 1461748 Hom.: 171786 Cov.: 48 AF XY: 0.483 AC XY: 351261 AN XY: 727176

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.299

Gnomad4 ASJ exome AF: 0.535

Gnomad4 EAS exome AF: 0.449

Gnomad4 SAS exome AF: 0.503

Gnomad4 FIN exome AF: 0.464

Gnomad4 NFE exome AF: 0.495

Gnomad4 OTH exome AF: 0.477

GnomAD4 genome AF: 0.397 AC: 60388 AN: 152012 Hom.: 13350 Cov.: 32 AF XY: 0.396 AC XY: 29389 AN XY: 74268

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.460

Alfa AF: 0.473 Hom.: 26175

Bravo AF: 0.379

Asia WGS AF: 0.482 AC: 1678 AN: 3478

EpiCase AF: 0.509

EpiControl AF: 0.518

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

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: Frequency -

Ciliary dyskinesia, primary, 40 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.10
DANN	Benign	0.28

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: rs8070256; hg19: chr17-11786951; COSMIC: COSV52335013; COSMIC: COSV52335013;