rs2286303

Variant names:

• chr17-11929970-A-G
• rs2286303
• NM_001372.4:c.11982A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-11929970-A-G
• chr17-11929970-A-T

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.11982A>G​(p.Pro3994Pro) 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 1,613,536 control chromosomes in the GnomAD database, including 77,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5576 hom., cov: 31)
  • Exomes 𝑓: 0.31 (72026 hom.)
• Consequence: DNAH9 NM_001372.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.51
• Publications: 18 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P
• 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=-0.79).
• BP6: Variant 17-11929970-A-G is Benign according to our data. Variant chr17-11929970-A-G is described in ClinVar as Benign. ClinVar VariationId is 402784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	NM_001372.4	MANE Select	c.11982A>G	p.Pro3994Pro	synonymous	Exon 63 of 69	NP_001363.2	Q9NYC9-1
	DNAH9	NM_004662.2		c.918A>G	p.Pro306Pro	synonymous	Exon 9 of 15	NP_004653.2	Q99499

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	ENST00000262442.9	TSL:1 MANE Select	c.11982A>G	p.Pro3994Pro	synonymous	Exon 63 of 69	ENSP00000262442.3	Q9NYC9-1
	DNAH9	ENST00000608377.5	TSL:1	c.918A>G	p.Pro306Pro	synonymous	Exon 9 of 15	ENSP00000476951.1	Q9NYC9-3
	DNAH9	ENST00000396001.6	TSL:1	n.1445A>G		non_coding_transcript_exon	Exon 9 of 15

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38808 AN: 151868 Hom.: 5574 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.292

GnomAD2 exomes AF: 0.285 AC: 71526 AN: 250620 AF XY: 0.294

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.200

Gnomad ASJ exome AF: 0.360

Gnomad EAS exome AF: 0.203

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.331

Gnomad OTH exome AF: 0.318

GnomAD4 exome AF: 0.310 AC: 452413 AN: 1461548 Hom.: 72026 Cov.: 37 AF XY: 0.312 AC XY: 226953 AN XY: 727034

African (AFR) AF: 0.0971 AC: 3250 AN: 33476

American (AMR) AF: 0.209 AC: 9340 AN: 44688

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

East Asian (EAS) AF: 0.165 AC: 6552 AN: 39688

South Asian (SAS) AF: 0.313 AC: 27017 AN: 86230

European-Finnish (FIN) AF: 0.319 AC: 17020 AN: 53412

Middle Eastern (MID) AF: 0.345 AC: 1990 AN: 5768

European-Non Finnish (NFE) AF: 0.324 AC: 359675 AN: 1111778

Other (OTH) AF: 0.302 AC: 18245 AN: 60382

GnomAD4 genome AF: 0.255 AC: 38810 AN: 151988 Hom.: 5576 Cov.: 31 AF XY: 0.256 AC XY: 19004 AN XY: 74278

African (AFR) AF: 0.107 AC: 4454 AN: 41496

American (AMR) AF: 0.253 AC: 3858 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1221 AN: 3466

East Asian (EAS) AF: 0.194 AC: 997 AN: 5146

South Asian (SAS) AF: 0.318 AC: 1528 AN: 4808

European-Finnish (FIN) AF: 0.317 AC: 3359 AN: 10582

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22458 AN: 67938

Other (OTH) AF: 0.291 AC: 609 AN: 2096

Alfa AF: 0.305 Hom.: 11686

Bravo AF: 0.240

Asia WGS AF: 0.238 AC: 826 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.14
DANN	Benign	0.65
PhyloP100		-1.5
Mutation Taster		=100/0	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: rs2286303; hg19: chr17-11833287; COSMIC: COSV52351486; COSMIC: COSV52351486;