17-78560729-C-T

Variant names:

• chr17-78560729-C-T
• rs78321431
• NM_173628.4:c.2031+11G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173628.4(DNAH17):​c.2031+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 1,544,228 control chromosomes in the GnomAD database, including 113,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (8737 hom., cov: 31)
  • Exomes 𝑓: 0.38 (105050 hom.)
• Consequence: DNAH17 NM_173628.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.497
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 17-78560729-C-T is Benign according to our data. Variant chr17-78560729-C-T is described in ClinVar as Benign. ClinVar VariationId is 402700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.521 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.2031+11G>A		intron	N/A	NP_775899.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.2031+11G>A		intron	N/A	ENSP00000374490.6
	DNAH17	ENST00000589793.1	TSL:2	n.1243+11G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49835 AN: 151922 Hom.: 8733 Cov.: 31

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.321

GnomAD2 exomes AF: 0.356 AC: 54398 AN: 153016 AF XY: 0.372

Gnomad AFR exome AF: 0.242

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.330

Gnomad EAS exome AF: 0.374

Gnomad FIN exome AF: 0.307

Gnomad NFE exome AF: 0.376

Gnomad OTH exome AF: 0.339

GnomAD4 exome AF: 0.383 AC: 533788 AN: 1392188 Hom.: 105050 Cov.: 38 AF XY: 0.388 AC XY: 265686 AN XY: 685482

African (AFR) AF: 0.238 AC: 7491 AN: 31514

American (AMR) AF: 0.217 AC: 7732 AN: 35554

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 8143 AN: 24938

East Asian (EAS) AF: 0.419 AC: 14927 AN: 35602

South Asian (SAS) AF: 0.543 AC: 42640 AN: 78516

European-Finnish (FIN) AF: 0.315 AC: 15399 AN: 48830

Middle Eastern (MID) AF: 0.351 AC: 1795 AN: 5120

European-Non Finnish (NFE) AF: 0.385 AC: 414099 AN: 1074386

Other (OTH) AF: 0.374 AC: 21562 AN: 57728

GnomAD4 genome AF: 0.328 AC: 49839 AN: 152040 Hom.: 8737 Cov.: 31 AF XY: 0.329 AC XY: 24411 AN XY: 74290

African (AFR) AF: 0.237 AC: 9838 AN: 41496

American (AMR) AF: 0.255 AC: 3895 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1142 AN: 3470

East Asian (EAS) AF: 0.387 AC: 1991 AN: 5148

South Asian (SAS) AF: 0.538 AC: 2591 AN: 4814

European-Finnish (FIN) AF: 0.312 AC: 3296 AN: 10556

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.380 AC: 25804 AN: 67974

Other (OTH) AF: 0.318 AC: 671 AN: 2112

Alfa AF: 0.351 Hom.: 14413

Bravo AF: 0.314

Asia WGS AF: 0.468 AC: 1627 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.53
DANN	Benign	0.75
PhyloP100		-0.50
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: rs78321431; hg19: chr17-76556811; COSMIC: COSV107503108;