17-11679772-T-C

Variant names:

• chr17-11679772-T-C
• rs8071438
• NM_001372.4:c.3369T>C

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.3369T>C​(p.Asp1123Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 1,613,704 control chromosomes in the GnomAD database, including 776,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71261 hom., cov: 32)
  • Exomes 𝑓: 0.98 (704758 hom.)
• Consequence: DNAH9 NM_001372.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.277
• Publications: 16 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=-0.84).
• BP6: Variant 17-11679772-T-C is Benign according to our data. Variant chr17-11679772-T-C is described in ClinVar as Benign. ClinVar VariationId is 402776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.277 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.982 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.3369T>C	p.Asp1123Asp	synonymous	Exon 18 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.3369T>C	p.Asp1123Asp	synonymous	Exon 18 of 69	ENSP00000262442.3	Q9NYC9-1
	DNAH9	ENST00000454412.6	TSL:5	c.3369T>C	p.Asp1123Asp	synonymous	Exon 18 of 68	ENSP00000414874.2	E7EP17

Frequencies

GnomAD3 genomes AF: 0.967 AC: 147142 AN: 152156 Hom.: 71210 Cov.: 32

Gnomad AFR AF: 0.929

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.971

Gnomad ASJ AF: 0.969

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.963

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.988

Gnomad OTH AF: 0.968

GnomAD2 exomes AF: 0.972 AC: 244454 AN: 251422 AF XY: 0.974

Gnomad AFR exome AF: 0.928

Gnomad AMR exome AF: 0.961

Gnomad ASJ exome AF: 0.968

Gnomad EAS exome AF: 0.912

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.989

Gnomad OTH exome AF: 0.979

GnomAD4 exome AF: 0.982 AC: 1434943 AN: 1461430 Hom.: 704758 Cov.: 40 AF XY: 0.982 AC XY: 713698 AN XY: 727070

African (AFR) AF: 0.929 AC: 31098 AN: 33468

American (AMR) AF: 0.963 AC: 43047 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 25292 AN: 26130

East Asian (EAS) AF: 0.906 AC: 35969 AN: 39692

South Asian (SAS) AF: 0.966 AC: 83349 AN: 86242

European-Finnish (FIN) AF: 0.999 AC: 53355 AN: 53414

Middle Eastern (MID) AF: 0.979 AC: 5646 AN: 5768

European-Non Finnish (NFE) AF: 0.988 AC: 1098277 AN: 1111618

Other (OTH) AF: 0.976 AC: 58910 AN: 60374

GnomAD4 genome AF: 0.967 AC: 147253 AN: 152274 Hom.: 71261 Cov.: 32 AF XY: 0.968 AC XY: 72015 AN XY: 74432

African (AFR) AF: 0.929 AC: 38586 AN: 41536

American (AMR) AF: 0.971 AC: 14844 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 3366 AN: 3472

East Asian (EAS) AF: 0.910 AC: 4708 AN: 5174

South Asian (SAS) AF: 0.964 AC: 4645 AN: 4820

European-Finnish (FIN) AF: 0.999 AC: 10607 AN: 10618

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.988 AC: 67252 AN: 68042

Other (OTH) AF: 0.967 AC: 2042 AN: 2112

Alfa AF: 0.980 Hom.: 98894

Bravo AF: 0.962

Asia WGS AF: 0.923 AC: 3211 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Ciliary dyskinesia, primary, 40 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.32
DANN	Benign	0.25
PhyloP100		0.28
Mutation Taster		=99/1	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: rs8071438; hg19: chr17-11583089; COSMIC: COSV52334757;