rs8070256

Variant names:

• chr17-11883634-T-C
• rs8070256
• ENST00000608377.5:c.-210T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000608377.5(DNAH9):​c.-210T>C variant causes a 5 prime UTR premature start codon gain 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 ENST00000608377.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.502
• Publications: 21 publications found

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]

DNAH9 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 40

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• schizophrenia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

LOC101928350 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 402783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000608377.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	NM_001372.4	MANE Select	c.10855T>C	p.Leu3619Leu	synonymous	Exon 56 of 69	NP_001363.2
	DNAH9	NM_004662.2		c.-210T>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 15	NP_004653.2
	DNAH9	NM_004662.2		c.-210T>C		5_prime_UTR	Exon 2 of 15	NP_004653.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	ENST00000608377.5	TSL:1	c.-210T>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 15	ENSP00000476951.1
	DNAH9	ENST00000262442.9	TSL:1 MANE Select	c.10855T>C	p.Leu3619Leu	synonymous	Exon 56 of 69	ENSP00000262442.3
	DNAH9	ENST00000396001.6	TSL:1	n.318T>C		non_coding_transcript_exon	Exon 2 of 15

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

GnomAD2 exomes AF: 0.448 AC: 112695 AN: 251360 AF XY: 0.463

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 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

African (AFR) AF: 0.180 AC: 6040 AN: 33480

American (AMR) AF: 0.299 AC: 13373 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 13973 AN: 26132

East Asian (EAS) AF: 0.449 AC: 17815 AN: 39698

South Asian (SAS) AF: 0.503 AC: 43366 AN: 86252

European-Finnish (FIN) AF: 0.464 AC: 24776 AN: 53414

Middle Eastern (MID) AF: 0.545 AC: 3140 AN: 5766

European-Non Finnish (NFE) AF: 0.495 AC: 550611 AN: 1111890

Other (OTH) AF: 0.477 AC: 28828 AN: 60392

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

African (AFR) AF: 0.188 AC: 7816 AN: 41480

American (AMR) AF: 0.378 AC: 5779 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1898 AN: 3466

East Asian (EAS) AF: 0.487 AC: 2503 AN: 5144

South Asian (SAS) AF: 0.518 AC: 2494 AN: 4812

European-Finnish (FIN) AF: 0.457 AC: 4822 AN: 10562

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33573 AN: 67958

Other (OTH) AF: 0.460 AC: 968 AN: 2106

Alfa AF: 0.464 Hom.: 63761

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.10
DANN	Benign	0.28
PhyloP100		-0.50
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

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