NM_173628.4:c.2547A>G

Variant names:

• chr17-78539866-T-C
• rs7221209
• NM_173628.4:c.2547A>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_173628.4(DNAH17):​c.2547A>G​(p.Leu849Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,596,024 control chromosomes in the GnomAD database, including 461,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (44625 hom., cov: 30)
  • Exomes 𝑓: 0.76 (416574 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.13
• Publications: 17 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=-0.9).
• BP6: Variant 17-78539866-T-C is Benign according to our data. Variant chr17-78539866-T-C is described in ClinVar as Benign. ClinVar VariationId is 402699.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.13 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 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.2547A>G	p.Leu849Leu	synonymous	Exon 18 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.2547A>G	p.Leu849Leu	synonymous	Exon 18 of 81	ENSP00000374490.6	Q9UFH2-1

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116282 AN: 151868 Hom.: 44580 Cov.: 30

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.776

GnomAD2 exomes AF: 0.754 AC: 175501 AN: 232736 AF XY: 0.754

Gnomad AFR exome AF: 0.786

Gnomad AMR exome AF: 0.710

Gnomad ASJ exome AF: 0.759

Gnomad EAS exome AF: 0.752

Gnomad FIN exome AF: 0.770

Gnomad NFE exome AF: 0.763

Gnomad OTH exome AF: 0.759

GnomAD4 exome AF: 0.759 AC: 1096377 AN: 1444038 Hom.: 416574 Cov.: 49 AF XY: 0.758 AC XY: 544319 AN XY: 717712

African (AFR) AF: 0.789 AC: 25680 AN: 32542

American (AMR) AF: 0.709 AC: 28486 AN: 40154

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 19286 AN: 25556

East Asian (EAS) AF: 0.787 AC: 31020 AN: 39410

South Asian (SAS) AF: 0.730 AC: 60388 AN: 82706

European-Finnish (FIN) AF: 0.775 AC: 40288 AN: 51960

Middle Eastern (MID) AF: 0.700 AC: 3986 AN: 5698

European-Non Finnish (NFE) AF: 0.761 AC: 841839 AN: 1106328

Other (OTH) AF: 0.761 AC: 45404 AN: 59684

GnomAD4 genome AF: 0.766 AC: 116377 AN: 151986 Hom.: 44625 Cov.: 30 AF XY: 0.766 AC XY: 56930 AN XY: 74294

African (AFR) AF: 0.784 AC: 32494 AN: 41446

American (AMR) AF: 0.728 AC: 11113 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2618 AN: 3470

East Asian (EAS) AF: 0.766 AC: 3947 AN: 5154

South Asian (SAS) AF: 0.733 AC: 3526 AN: 4810

European-Finnish (FIN) AF: 0.759 AC: 8027 AN: 10570

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52046 AN: 67958

Other (OTH) AF: 0.769 AC: 1620 AN: 2106

Alfa AF: 0.759 Hom.: 21504

Bravo AF: 0.763

Asia WGS AF: 0.767 AC: 2666 AN: 3478

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	-0.90
CADD	Benign	0.65
DANN	Benign	0.36
PhyloP100		-1.1
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: rs7221209; hg19: chr17-76535948; COSMIC: COSV67751209; COSMIC: COSV67751209;