17-11598497-C-T

Variant names:

• chr17-11598497-C-T
• rs12604013
• NM_001372.4:c.-2C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001372.4(DNAH9):​c.-2C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,366,578 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0041 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (170 hom.)
• Consequence: DNAH9 NM_001372.4 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.147
• Publications: 2 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 17-11598497-C-T is Benign according to our data. Variant chr17-11598497-C-T is described in ClinVar as Benign. ClinVar VariationId is 3044413.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0748 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.-2C>T		5_prime_UTR	Exon 1 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.-2C>T		5_prime_UTR	Exon 1 of 69	ENSP00000262442.3	Q9NYC9-1
	DNAH9	ENST00000579406.1	TSL:1	n.26C>T		non_coding_transcript_exon	Exon 1 of 8
	DNAH9	ENST00000579828.5	TSL:2	c.-2C>T		5_prime_UTR	Exon 1 of 4	ENSP00000463782.1	J3QQK8

Frequencies

GnomAD3 genomes AF: 0.00406 AC: 617 AN: 152150 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0811

Gnomad SAS AF: 0.0211

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.0182 AC: 87 AN: 4784 AF XY: 0.0174

Gnomad AFR exome AF: 0.00360

Gnomad AMR exome AF: 0.00112

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.149

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000491

Gnomad OTH exome AF: 0.00833

GnomAD4 exome AF: 0.00326 AC: 3954 AN: 1214310 Hom.: 170 Cov.: 33 AF XY: 0.00346 AC XY: 2038 AN XY: 589494

African (AFR) AF: 0.000209 AC: 5 AN: 23886

American (AMR) AF: 0.0000989 AC: 1 AN: 10110

Ashkenazi Jewish (ASJ) AF: 0.000412 AC: 7 AN: 16978

East Asian (EAS) AF: 0.0918 AC: 2537 AN: 27626

South Asian (SAS) AF: 0.0157 AC: 818 AN: 52102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28936

Middle Eastern (MID) AF: 0.000856 AC: 3 AN: 3506

European-Non Finnish (NFE) AF: 0.0000999 AC: 100 AN: 1001302

Other (OTH) AF: 0.00969 AC: 483 AN: 49864

GnomAD4 genome AF: 0.00407 AC: 619 AN: 152268 Hom.: 23 Cov.: 32 AF XY: 0.00430 AC XY: 320 AN XY: 74450

African (AFR) AF: 0.000649 AC: 27 AN: 41580

American (AMR) AF: 0.00222 AC: 34 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.0813 AC: 418 AN: 5144

South Asian (SAS) AF: 0.0209 AC: 101 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68004

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.0000696 Hom.: 0

Bravo AF: 0.00398

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DNAH9-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.3
DANN	Benign	0.88
PhyloP100		-0.15
PromoterAI		0.13	Neutral
Mutation Taster		=300/0	polymorphism

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: rs12604013; hg19: chr17-11501814;