NM_001372.4:c.1452A>G

Variant names:

• chr17-11629518-A-G
• rs9895535
• NM_001372.4:c.1452A>G

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.1452A>G​(p.Glu484Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,613,356 control chromosomes in the GnomAD database, including 88,842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (15692 hom., cov: 32)
  • Exomes 𝑓: 0.31 (73150 hom.)
• Consequence: DNAH9 NM_001372.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.516
• Publications: 12 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=-0.91).
• BP6: Variant 17-11629518-A-G is Benign according to our data. Variant chr17-11629518-A-G is described in ClinVar as Benign. ClinVar VariationId is 402774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.516 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 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.1452A>G	p.Glu484Glu	synonymous	Exon 7 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.1452A>G	p.Glu484Glu	synonymous	Exon 7 of 69	ENSP00000262442.3	Q9NYC9-1
	DNAH9	ENST00000579406.1	TSL:1	n.1479A>G		non_coding_transcript_exon	Exon 7 of 8
	DNAH9	ENST00000454412.6	TSL:5	c.1452A>G	p.Glu484Glu	synonymous	Exon 7 of 68	ENSP00000414874.2	E7EP17

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62548 AN: 151896 Hom.: 15649 Cov.: 32

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.337

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.364

GnomAD2 exomes AF: 0.312 AC: 78383 AN: 251362 AF XY: 0.308

Gnomad AFR exome AF: 0.732

Gnomad AMR exome AF: 0.220

Gnomad ASJ exome AF: 0.255

Gnomad EAS exome AF: 0.145

Gnomad FIN exome AF: 0.367

Gnomad NFE exome AF: 0.300

Gnomad OTH exome AF: 0.309

GnomAD4 exome AF: 0.305 AC: 446383 AN: 1461338 Hom.: 73150 Cov.: 34 AF XY: 0.304 AC XY: 220830 AN XY: 727014

African (AFR) AF: 0.741 AC: 24790 AN: 33462

American (AMR) AF: 0.229 AC: 10248 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 6659 AN: 26130

East Asian (EAS) AF: 0.138 AC: 5482 AN: 39696

South Asian (SAS) AF: 0.312 AC: 26903 AN: 86220

European-Finnish (FIN) AF: 0.357 AC: 19057 AN: 53390

Middle Eastern (MID) AF: 0.291 AC: 1674 AN: 5758

European-Non Finnish (NFE) AF: 0.299 AC: 332094 AN: 1111576

Other (OTH) AF: 0.323 AC: 19476 AN: 60386

GnomAD4 genome AF: 0.412 AC: 62645 AN: 152018 Hom.: 15692 Cov.: 32 AF XY: 0.411 AC XY: 30528 AN XY: 74322

African (AFR) AF: 0.712 AC: 29514 AN: 41448

American (AMR) AF: 0.292 AC: 4464 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 934 AN: 3470

East Asian (EAS) AF: 0.147 AC: 756 AN: 5154

South Asian (SAS) AF: 0.323 AC: 1557 AN: 4818

European-Finnish (FIN) AF: 0.375 AC: 3962 AN: 10574

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20328 AN: 67962

Other (OTH) AF: 0.366 AC: 772 AN: 2110

Alfa AF: 0.354 Hom.: 5686

Bravo AF: 0.417

Asia WGS AF: 0.310 AC: 1078 AN: 3478

EpiCase AF: 0.302

EpiControl AF: 0.305

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.45
PhyloP100		-0.52
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9895535; hg19: chr17-11532835; COSMIC: COSV52333211;