rs1859887

Variant names:

• chr17-11930048-G-A
• rs1859887
• NM_001372.4:c.12060G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001372.4(DNAH9):​c.12060G>A​(p.Thr4020Thr) 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 1,613,610 control chromosomes in the GnomAD database, including 77,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5567 hom., cov: 31)
  • Exomes 𝑓: 0.31 (71748 hom.)
• Consequence: DNAH9 NM_001372.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -5.21
• Publications: 15 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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 17-11930048-G-A is Benign according to our data. Variant chr17-11930048-G-A is described in ClinVar as Benign. ClinVar VariationId is 402785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH9	NM_001372.4	c.12060G>A	p.Thr4020Thr	synonymous_variant	Exon 63 of 69	ENST00000262442.9	NP_001363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH9	ENST00000262442.9	c.12060G>A	p.Thr4020Thr	synonymous_variant	Exon 63 of 69	1	NM_001372.4	ENSP00000262442.3
DNAH9	ENST00000608377.5	c.996G>A	p.Thr332Thr	synonymous_variant	Exon 9 of 15	1		ENSP00000476951.1
DNAH9	ENST00000396001.6	n.1523G>A		non_coding_transcript_exon_variant	Exon 9 of 15	1
DNAH9	ENST00000454412.6	c.11878-1966G>A		intron_variant	Intron 62 of 67	5		ENSP00000414874.2

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38763 AN: 151868 Hom.: 5565 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.291

GnomAD2 exomes AF: 0.285 AC: 71418 AN: 250712 AF XY: 0.293

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.199

Gnomad ASJ exome AF: 0.361

Gnomad EAS exome AF: 0.202

Gnomad FIN exome AF: 0.317

Gnomad NFE exome AF: 0.330

Gnomad OTH exome AF: 0.317

GnomAD4 exome AF: 0.309 AC: 451515 AN: 1461622 Hom.: 71748 Cov.: 39 AF XY: 0.312 AC XY: 226515 AN XY: 727104

African (AFR) AF: 0.0966 AC: 3234 AN: 33476

American (AMR) AF: 0.209 AC: 9331 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 9324 AN: 26126

East Asian (EAS) AF: 0.164 AC: 6517 AN: 39692

South Asian (SAS) AF: 0.313 AC: 27006 AN: 86240

European-Finnish (FIN) AF: 0.318 AC: 16980 AN: 53396

Middle Eastern (MID) AF: 0.343 AC: 1981 AN: 5768

European-Non Finnish (NFE) AF: 0.323 AC: 358923 AN: 1111838

Other (OTH) AF: 0.302 AC: 18219 AN: 60388

GnomAD4 genome AF: 0.255 AC: 38764 AN: 151988 Hom.: 5567 Cov.: 31 AF XY: 0.256 AC XY: 18982 AN XY: 74268

African (AFR) AF: 0.107 AC: 4448 AN: 41496

American (AMR) AF: 0.253 AC: 3856 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1225 AN: 3470

East Asian (EAS) AF: 0.194 AC: 995 AN: 5134

South Asian (SAS) AF: 0.317 AC: 1525 AN: 4808

European-Finnish (FIN) AF: 0.318 AC: 3351 AN: 10554

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22432 AN: 67952

Other (OTH) AF: 0.290 AC: 610 AN: 2104

Alfa AF: 0.296 Hom.: 3120

Bravo AF: 0.240

Asia WGS AF: 0.237 AC: 821 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

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

- -

-

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: MAF -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.31
DANN	Benign	0.65
PhyloP100		-5.2
Mutation Taster		=89/11	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: rs1859887; hg19: chr17-11833365; COSMIC: COSV52341635; COSMIC: COSV52341635;