chr17-78476686-G-A

Variant names:

• chr17-78476686-G-A
• rs7405830
• NM_173628.4:c.8040C>T

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.8040C>T​(p.Leu2680Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,611,882 control chromosomes in the GnomAD database, including 51,979 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (12352 hom., cov: 32)
  • Exomes 𝑓: 0.22 (39627 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.67
• Publications: 21 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=-0.72).
• BP6: Variant 17-78476686-G-A is Benign according to our data. Variant chr17-78476686-G-A is described in ClinVar as Benign. ClinVar VariationId is 402679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.67 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 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.8040C>T	p.Leu2680Leu	synonymous	Exon 52 of 81	NP_775899.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.8040C>T	p.Leu2680Leu	synonymous	Exon 52 of 81	ENSP00000374490.6
	DNAH17	ENST00000586052.5	TSL:5	n.1511-827C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52246 AN: 151914 Hom.: 12314 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.323

GnomAD2 exomes AF: 0.249 AC: 61240 AN: 246036 AF XY: 0.243

Gnomad AFR exome AF: 0.695

Gnomad AMR exome AF: 0.230

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.289

Gnomad FIN exome AF: 0.206

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.229

GnomAD4 exome AF: 0.218 AC: 318529 AN: 1459850 Hom.: 39627 Cov.: 33 AF XY: 0.217 AC XY: 157603 AN XY: 726002

African (AFR) AF: 0.696 AC: 23291 AN: 33460

American (AMR) AF: 0.231 AC: 10254 AN: 44384

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 5091 AN: 26092

East Asian (EAS) AF: 0.242 AC: 9588 AN: 39642

South Asian (SAS) AF: 0.247 AC: 21255 AN: 85886

European-Finnish (FIN) AF: 0.207 AC: 11046 AN: 53292

Middle Eastern (MID) AF: 0.228 AC: 1314 AN: 5762

European-Non Finnish (NFE) AF: 0.200 AC: 222073 AN: 1111008

Other (OTH) AF: 0.242 AC: 14617 AN: 60324

GnomAD4 genome AF: 0.344 AC: 52330 AN: 152032 Hom.: 12352 Cov.: 32 AF XY: 0.342 AC XY: 25397 AN XY: 74338

African (AFR) AF: 0.682 AC: 28247 AN: 41428

American (AMR) AF: 0.265 AC: 4051 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 701 AN: 3472

East Asian (EAS) AF: 0.281 AC: 1457 AN: 5176

South Asian (SAS) AF: 0.244 AC: 1176 AN: 4816

European-Finnish (FIN) AF: 0.207 AC: 2190 AN: 10588

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13585 AN: 67968

Other (OTH) AF: 0.324 AC: 682 AN: 2108

Alfa AF: 0.249 Hom.: 25444

Bravo AF: 0.364

Asia WGS AF: 0.306 AC: 1067 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.72
CADD	Benign	0.094
DANN	Benign	0.57
PhyloP100		-2.7
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs7405830; hg19: chr17-76472768; COSMIC: COSV67754473; COSMIC: COSV67754473;