rs12449553

Variant names:

• chr17-11854239-C-G
• rs12449553
• NM_001372.4:c.9744C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-11854239-C-G
• chr17-11854239-C-T
• chr17-11854239-C-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.9744C>G​(p.Pro3248Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 1,613,906 control chromosomes in the GnomAD database, including 141,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P3248P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.40 (12611 hom., cov: 32)
  • Exomes 𝑓: 0.42 (128397 hom.)
• Consequence: DNAH9 NM_001372.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -4.91
• Publications: 20 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=-0.89).
• BP6: Variant 17-11854239-C-G is Benign according to our data. Variant chr17-11854239-C-G is described in ClinVar as Benign. ClinVar VariationId is 402782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.54 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.9744C>G	p.Pro3248Pro	synonymous	Exon 50 of 69	NP_001363.2	Q9NYC9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	ENST00000262442.9	TSL:1 MANE Select	c.9744C>G	p.Pro3248Pro	synonymous	Exon 50 of 69	ENSP00000262442.3	Q9NYC9-1
	DNAH9	ENST00000454412.6	TSL:5	c.9744C>G	p.Pro3248Pro	synonymous	Exon 50 of 68	ENSP00000414874.2	E7EP17
	DNAH9	ENST00000579703.1	TSL:3	c.186C>G	p.Pro62Pro	synonymous	Exon 1 of 4	ENSP00000463622.2	J3QLM9

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60887 AN: 151906 Hom.: 12601 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.417

GnomAD2 exomes AF: 0.432 AC: 108654 AN: 251438 AF XY: 0.424

Gnomad AFR exome AF: 0.324

Gnomad AMR exome AF: 0.663

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.378

Gnomad FIN exome AF: 0.406

Gnomad NFE exome AF: 0.405

Gnomad OTH exome AF: 0.434

GnomAD4 exome AF: 0.416 AC: 607421 AN: 1461882 Hom.: 128397 Cov.: 71 AF XY: 0.413 AC XY: 300160 AN XY: 727246

African (AFR) AF: 0.322 AC: 10797 AN: 33480

American (AMR) AF: 0.649 AC: 29016 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 9232 AN: 26136

East Asian (EAS) AF: 0.356 AC: 14152 AN: 39700

South Asian (SAS) AF: 0.402 AC: 34714 AN: 86258

European-Finnish (FIN) AF: 0.402 AC: 21477 AN: 53420

Middle Eastern (MID) AF: 0.388 AC: 2236 AN: 5768

European-Non Finnish (NFE) AF: 0.415 AC: 461627 AN: 1112000

Other (OTH) AF: 0.400 AC: 24170 AN: 60396

GnomAD4 genome AF: 0.401 AC: 60921 AN: 152024 Hom.: 12611 Cov.: 32 AF XY: 0.400 AC XY: 29734 AN XY: 74338

African (AFR) AF: 0.333 AC: 13804 AN: 41450

American (AMR) AF: 0.549 AC: 8395 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1287 AN: 3470

East Asian (EAS) AF: 0.367 AC: 1897 AN: 5168

South Asian (SAS) AF: 0.407 AC: 1961 AN: 4818

European-Finnish (FIN) AF: 0.411 AC: 4345 AN: 10562

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27920 AN: 67968

Other (OTH) AF: 0.415 AC: 875 AN: 2106

Alfa AF: 0.319 Hom.: 1327

Bravo AF: 0.409

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Ciliary dyskinesia, primary, 40 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.043
DANN	Benign	0.47
PhyloP100		-4.9
PromoterAI		0.0060	Neutral
Mutation Taster		=86/14	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: rs12449553; hg19: chr17-11757556; COSMIC: COSV52335004;