rs691225

Variant names:

• chr17-78466688-G-A
• rs691225
• NM_173628.4:c.8907C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-78466688-G-A
• chr17-78466688-G-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_173628.4(DNAH17):​c.8907C>T​(p.Ser2969Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 1,611,012 control chromosomes in the GnomAD database, including 468,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (36293 hom., cov: 31)
  • Exomes 𝑓: 0.77 (432348 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.209
• Publications: 16 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-78466688-G-A is Benign according to our data. Variant chr17-78466688-G-A is described in ClinVar as Benign. ClinVar VariationId is 402677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.209 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	NM_173628.4	MANE Select	c.8907C>T	p.Ser2969Ser	synonymous	Exon 56 of 81	NP_775899.3	Q9UFH2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.8907C>T	p.Ser2969Ser	synonymous	Exon 56 of 81	ENSP00000374490.6	Q9UFH2-1
	DNAH17	ENST00000586052.5	TSL:5	n.2289C>T		non_coding_transcript_exon	Exon 12 of 35
	DNAH17	ENST00000591369.5	TSL:5	n.507C>T		non_coding_transcript_exon	Exon 3 of 28	ENSP00000466150.1	K7ELN3

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101790 AN: 151894 Hom.: 36283 Cov.: 31

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.708

GnomAD2 exomes AF: 0.738 AC: 181658 AN: 246148 AF XY: 0.737

Gnomad AFR exome AF: 0.387

Gnomad AMR exome AF: 0.779

Gnomad ASJ exome AF: 0.765

Gnomad EAS exome AF: 0.822

Gnomad FIN exome AF: 0.757

Gnomad NFE exome AF: 0.782

Gnomad OTH exome AF: 0.773

GnomAD4 exome AF: 0.766 AC: 1117628 AN: 1459000 Hom.: 432348 Cov.: 54 AF XY: 0.763 AC XY: 553377 AN XY: 725678

African (AFR) AF: 0.392 AC: 13014 AN: 33238

American (AMR) AF: 0.778 AC: 34646 AN: 44558

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 19946 AN: 26076

East Asian (EAS) AF: 0.819 AC: 32391 AN: 39556

South Asian (SAS) AF: 0.626 AC: 53778 AN: 85944

European-Finnish (FIN) AF: 0.754 AC: 39727 AN: 52680

Middle Eastern (MID) AF: 0.780 AC: 4491 AN: 5758

European-Non Finnish (NFE) AF: 0.787 AC: 874202 AN: 1110896

Other (OTH) AF: 0.754 AC: 45433 AN: 60294

GnomAD4 genome AF: 0.670 AC: 101822 AN: 152012 Hom.: 36293 Cov.: 31 AF XY: 0.670 AC XY: 49750 AN XY: 74294

African (AFR) AF: 0.404 AC: 16749 AN: 41440

American (AMR) AF: 0.762 AC: 11641 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2651 AN: 3472

East Asian (EAS) AF: 0.830 AC: 4269 AN: 5146

South Asian (SAS) AF: 0.622 AC: 2993 AN: 4812

European-Finnish (FIN) AF: 0.752 AC: 7955 AN: 10574

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.783 AC: 53212 AN: 67978

Other (OTH) AF: 0.710 AC: 1500 AN: 2112

Alfa AF: 0.731 Hom.: 31795

Bravo AF: 0.661

Asia WGS AF: 0.705 AC: 2448 AN: 3478

EpiCase AF: 0.780

EpiControl AF: 0.779

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	DNAH17-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.037
DANN	Benign	0.34
PhyloP100		-0.21
Mutation Taster		=96/4	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: rs691225; hg19: chr17-76462770; COSMIC: COSV67755373;