rs72920970

Variant names:

• chr17-78569259-G-A
• rs72920970
• NM_173628.4:c.1198-7C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-78569259-G-A
• chr17-78569259-G-C

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.1198-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,599,836 control chromosomes in the GnomAD database, including 93,892 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7757 hom., cov: 32)
  • Exomes 𝑓: 0.34 (86135 hom.)
• Consequence: DNAH17 NM_173628.4 splice_region, intron
• Scores: Splicing: ADA: 0.00003716
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0270
• Publications: 7 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=-0.86).
• BP6: Variant 17-78569259-G-A is Benign according to our data. Variant chr17-78569259-G-A is described in ClinVar as Benign. ClinVar VariationId is 402702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.442 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.1198-7C>T		splice_region 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.1198-7C>T		splice_region intron	N/A	ENSP00000374490.6
	DNAH17	ENST00000589793.1	TSL:2	n.410-7C>T		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46811 AN: 152028 Hom.: 7748 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.318

GnomAD2 exomes AF: 0.340 AC: 77264 AN: 227336 AF XY: 0.331

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.519

Gnomad ASJ exome AF: 0.294

Gnomad EAS exome AF: 0.306

Gnomad FIN exome AF: 0.344

Gnomad NFE exome AF: 0.339

Gnomad OTH exome AF: 0.349

GnomAD4 exome AF: 0.340 AC: 492420 AN: 1447690 Hom.: 86135 Cov.: 34 AF XY: 0.337 AC XY: 241930 AN XY: 718836

African (AFR) AF: 0.191 AC: 6362 AN: 33290

American (AMR) AF: 0.514 AC: 21630 AN: 42078

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 7556 AN: 25778

East Asian (EAS) AF: 0.278 AC: 10921 AN: 39330

South Asian (SAS) AF: 0.244 AC: 20452 AN: 83940

European-Finnish (FIN) AF: 0.344 AC: 18114 AN: 52652

Middle Eastern (MID) AF: 0.346 AC: 1991 AN: 5756

European-Non Finnish (NFE) AF: 0.349 AC: 385502 AN: 1104946

Other (OTH) AF: 0.332 AC: 19892 AN: 59920

GnomAD4 genome AF: 0.308 AC: 46849 AN: 152146 Hom.: 7757 Cov.: 32 AF XY: 0.309 AC XY: 23006 AN XY: 74376

African (AFR) AF: 0.202 AC: 8366 AN: 41504

American (AMR) AF: 0.451 AC: 6885 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 993 AN: 3470

East Asian (EAS) AF: 0.295 AC: 1524 AN: 5158

South Asian (SAS) AF: 0.244 AC: 1178 AN: 4828

European-Finnish (FIN) AF: 0.341 AC: 3611 AN: 10592

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23298 AN: 67990

Other (OTH) AF: 0.322 AC: 681 AN: 2116

Alfa AF: 0.320 Hom.: 5248

Bravo AF: 0.314

Asia WGS AF: 0.250 AC: 867 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	-0.86
CADD	Benign	2.7
DANN	Benign	0.36
PhyloP100		0.027
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000037
dbscSNV1_RF	Benign	0.0
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: rs72920970; hg19: chr17-76565341; COSMIC: COSV67755653;