rs2028734

chr17-78500410-A-Gchr17-78500410-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_173628.4(DNAH17):c.5535T>C(p.Pro1845=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,610,380 control chromosomes in the GnomAD database, including 563,323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (57830 hom., cov: 32)
  • Exomes 𝑓: 0.83 (505493 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.27

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-AS1 (HGNC:48594): (DNAH17 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-78500410-A-G is Benign according to our data. Variant chr17-78500410-A-G is described in ClinVar as [Benign]. Clinvar id is 402685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.27 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH17	NM_173628.4	c.5535T>C	p.Pro1845=	synonymous_variant	36/81	ENST00000389840.7
DNAH17-AS1	NR_102401.1	n.2517A>G		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH17	ENST00000389840.7	c.5535T>C	p.Pro1845=	synonymous_variant	36/81	5	NM_173628.4	P1
DNAH17-AS1	ENST00000598378.2	n.1951A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.868 AC: 132048 AN: 152106 Hom.: 57768 Cov.: 32

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.872

GnomAD3 exomes AF: 0.862 AC: 209785 AN: 243284 Hom.: 91093 AF XY: 0.860 AC XY: 114070 AN XY: 132710

Gnomad AFR exome AF: 0.970

Gnomad AMR exome AF: 0.916

Gnomad ASJ exome AF: 0.846

Gnomad EAS exome AF: 0.977

Gnomad SAS exome AF: 0.928

Gnomad FIN exome AF: 0.809

Gnomad NFE exome AF: 0.807

Gnomad OTH exome AF: 0.845

GnomAD4 exome AF: 0.831 AC: 1211882 AN: 1458156 Hom.: 505493 Cov.: 54 AF XY: 0.832 AC XY: 603747 AN XY: 725336

Gnomad4 AFR exome AF: 0.975

Gnomad4 AMR exome AF: 0.913

Gnomad4 ASJ exome AF: 0.843

Gnomad4 EAS exome AF: 0.988

Gnomad4 SAS exome AF: 0.926

Gnomad4 FIN exome AF: 0.809

Gnomad4 NFE exome AF: 0.810

Gnomad4 OTH exome AF: 0.850

GnomAD4 genome AF: 0.868 AC: 132169 AN: 152224 Hom.: 57830 Cov.: 32 AF XY: 0.871 AC XY: 64815 AN XY: 74416

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.877

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.978

Gnomad4 SAS AF: 0.931

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.804

Gnomad4 OTH AF: 0.873

Alfa AF: 0.831 Hom.: 29337

Bravo AF: 0.878

Asia WGS AF: 0.965 AC: 3357 AN: 3478

EpiCase AF: 0.805

EpiControl AF: 0.811

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.042
Dann	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs2028734; hg19: chr17-76496492;