NM_001372.4:c.1810A>G

Variant names:

• chr17-11640293-A-G
• rs61740059
• NM_001372.4:c.1810A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001372.4(DNAH9):​c.1810A>G​(p.Met604Val) variant causes a missense change. The variant allele was found at a frequency of 0.0257 in 1,613,072 control chromosomes in the GnomAD database, including 689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (58 hom., cov: 32)
  • Exomes 𝑓: 0.026 (631 hom.)
• Consequence: DNAH9 NM_001372.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.88

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011774987).
• BP6: Variant 17-11640293-A-G is Benign according to our data. Variant chr17-11640293-A-G is described in ClinVar as [Benign]. Clinvar id is 402775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-11640293-A-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0203 (3098/152300) while in subpopulation SAS AF= 0.0304 (147/4828). AF 95% confidence interval is 0.0278. There are 58 homozygotes in gnomad4. There are 1426 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH9	NM_001372.4	c.1810A>G	p.Met604Val	missense_variant	Exon 10 of 69	ENST00000262442.9	NP_001363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH9	ENST00000262442.9	c.1810A>G	p.Met604Val	missense_variant	Exon 10 of 69	1	NM_001372.4	ENSP00000262442.3
DNAH9	ENST00000454412.6	c.1810A>G	p.Met604Val	missense_variant	Exon 10 of 68	5		ENSP00000414874.2

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3099 AN: 152182 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.00507

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0302

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0289

Gnomad OTH AF: 0.0302

GnomAD3 exomes AF: 0.0232 AC: 5834 AN: 251188 Hom.: 93 AF XY: 0.0251 AC XY: 3412 AN XY: 135776

Gnomad AFR exome AF: 0.00437

Gnomad AMR exome AF: 0.0108

Gnomad ASJ exome AF: 0.0440

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0304

Gnomad FIN exome AF: 0.0226

Gnomad NFE exome AF: 0.0296

Gnomad OTH exome AF: 0.0258

GnomAD4 exome AF: 0.0263 AC: 38398 AN: 1460772 Hom.: 631 Cov.: 31 AF XY: 0.0269 AC XY: 19568 AN XY: 726748

Gnomad4 AFR exome AF: 0.00404

Gnomad4 AMR exome AF: 0.0117

Gnomad4 ASJ exome AF: 0.0440

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0322

Gnomad4 FIN exome AF: 0.0222

Gnomad4 NFE exome AF: 0.0278

Gnomad4 OTH exome AF: 0.0241

GnomAD4 genome AF: 0.0203 AC: 3098 AN: 152300 Hom.: 58 Cov.: 32 AF XY: 0.0192 AC XY: 1426 AN XY: 74460

Gnomad4 AFR AF: 0.00505

Gnomad4 AMR AF: 0.0184

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0304

Gnomad4 FIN AF: 0.0219

Gnomad4 NFE AF: 0.0289

Gnomad4 OTH AF: 0.0294

Alfa AF: 0.0285 Hom.: 112

Bravo AF: 0.0196

TwinsUK AF: 0.0286 AC: 106

ALSPAC AF: 0.0278 AC: 107

ESP6500AA AF: 0.00363 AC: 16

ESP6500EA AF: 0.0322 AC: 277

ExAC AF: 0.0236 AC: 2863

Asia WGS AF: 0.0120 AC: 41 AN: 3478

EpiCase AF: 0.0300

EpiControl AF: 0.0290

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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: Candidate PCD gene, but frequency is high -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D;D
MetaRNN	Benign	0.012	T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Uncertain	0.38
Sift	Benign	0.033	D;D
Polyphen		0.95	P;.
Vest4		0.13
MPC		0.14
ClinPred		0.026	T
GERP RS		5.4
Varity_R		0.45
gMVP		0.38

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: rs61740059; hg19: chr17-11543610; COSMIC: COSV105866163;