chr17-11679772-T-G

Variant names:

• chr17-11679772-T-G
• NM_001372.4:c.3369T>G
• DNAH9 p.Asp1123Glu

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

0 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 0 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Moderate

The NM_001372.4(DNAH9):c.3369T>G (p.Asp1123Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.D1123= (synonymous): Benign (ClinVar VariationId 402776, 2 stars)

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH9 NM_001372.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277
• Publications: 0 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: ClinGen, G2P, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 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

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 0 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD+AR) (base 0.0001, raised to 0.0005 by highest known P/LP ClinVar AF 0.000629) — PM2 moderate.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001372.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	DNAH9 NM_001372.4	MANE Select	c.3369T>G p.Asp1123Glu	missense	Exon 18 of 69	Prot: NP_001363.2 UniProt:

DNAH9 NM_001372.4

MANE Select

HGVSc / HGVSpc.3369T>Gp.Asp1123Glu

Exon rankExon 18 of 69

missense

Prot: NP_001363.2UniProt: Q9NYC9-1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	DNAH9 ENST00000262442.9	TSL:1MANE Select	c.3369T>G p.Asp1123Glu	missense	Exon 18 of 69	Prot: ENSP00000262442.3 UniProt:
	DNAH9 ENST00000454412.6	TSL:5	c.3369T>G p.Asp1123Glu	missense	Exon 18 of 68	Prot: ENSP00000414874.2 UniProt:

DNAH9 ENST00000262442.9

TSL:1MANE Select

HGVSc / HGVSpc.3369T>Gp.Asp1123Glu

Exon rankExon 18 of 69

missense

Prot: ENSP00000262442.3UniProt: Q9NYC9-1

DNAH9 ENST00000454412.6

TSL:5

HGVSc / HGVSpc.3369T>Gp.Asp1123Glu

Exon rankExon 18 of 68

missense

Prot: ENSP00000414874.2UniProt: E7EP17

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 exome	AF:	AC:	Hom:	AN:	Cov:40
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	1.5
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.22
DANN	Benign	0.13
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.24	N
FuncVEP CTI	Benign	0.0030
GPN-Star LLR	N/A	3.4
GPN-Star score	N/A	-1.1
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.99	T
Mutation Taster	N/A	94/6	polymorphism
MutationAssessor	Benign	-1.8	N
PhyloP100	Benign	0.28
PrimateAI	Benign	0.34	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.039
Sift	Benign	1.0	T
Varity_R	N/A	0.030
VESM-3B	Benign	-3.7

Showing 26 of 26 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

hg19: chr17-11583089;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar