17-78553070-C-G

Variant names:

• chr17-78553070-C-G
• rs8080186
• NM_173628.4:c.2179-265G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173628.4(DNAH17):​c.2179-265G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,606 control chromosomes in the GnomAD database, including 12,764 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (12764 hom., cov: 29)
• Consequence: DNAH17 NM_173628.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 3 publications found

Genes affected

DNAH17 (HGNC:2946): (dynein axonemal heavy chain 17) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. DNAH17 is a heavy chain associated with axonemal dynein (Milisav and Affara, 1998 [PubMed 9545504]).[supplied by OMIM, Mar 2008]

DNAH17 Gene-Disease associations (from GenCC):

• spermatogenic failure 39

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173628.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	NM_173628.4	MANE Select	c.2179-265G>C		intron	N/A	NP_775899.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.2179-265G>C		intron	N/A	ENSP00000374490.6
	DNAH17	ENST00000589793.1	TSL:2	n.1391-265G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61860 AN: 151488 Hom.: 12749 Cov.: 29

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.426

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.408 AC: 61912 AN: 151606 Hom.: 12764 Cov.: 29 AF XY: 0.404 AC XY: 29902 AN XY: 74052

African (AFR) AF: 0.377 AC: 15570 AN: 41272

American (AMR) AF: 0.373 AC: 5682 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1477 AN: 3472

East Asian (EAS) AF: 0.515 AC: 2634 AN: 5118

South Asian (SAS) AF: 0.386 AC: 1851 AN: 4800

European-Finnish (FIN) AF: 0.334 AC: 3518 AN: 10524

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29782 AN: 67890

Other (OTH) AF: 0.423 AC: 892 AN: 2108

Alfa AF: 0.409 Hom.: 1542

Bravo AF: 0.411

Asia WGS AF: 0.433 AC: 1506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.42
PhyloP100		-0.51
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: rs8080186; hg19: chr17-76549152;