chr17-78569259-G-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.1198-7C>T		splice_region_variant, intron_variant	Intron 8 of 80	ENST00000389840.7	NP_775899.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.1198-7C>T		splice_region_variant, intron_variant	Intron 8 of 80	5	NM_173628.4	ENSP00000374490.6
DNAH17	ENST00000589793.1	n.410-7C>T		splice_region_variant, intron_variant	Intron 4 of 12	2

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

GnomAD3 exomes AF: 0.340 AC: 77264 AN: 227336 Hom.: 13896 AF XY: 0.331 AC XY: 40561 AN XY: 122490

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 SAS exome AF: 0.242

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

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.514

Gnomad4 ASJ exome AF: 0.293

Gnomad4 EAS exome AF: 0.278

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.344

Gnomad4 NFE exome AF: 0.349

Gnomad4 OTH exome AF: 0.332

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

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.322

Alfa AF: 0.320 Hom.: 3940

Bravo AF: 0.314

Asia WGS AF: 0.250 AC: 867 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

DNAH17-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs72920970; hg19: chr17-76565341; COSMIC: COSV67755653;