rs61746438

chr17-78475284-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_173628.4(DNAH17):c.8505C>T(p.Asp2835=) variant causes a synonymous change. The variant allele was found at a frequency of 0.123 in 1,613,812 control chromosomes in the GnomAD database, including 13,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1129 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11963 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.10

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 17-78475284-G-A is Benign according to our data. Variant chr17-78475284-G-A is described in ClinVar as [Benign]. Clinvar id is 402678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH17	NM_173628.4	c.8505C>T	p.Asp2835=	synonymous_variant	54/81	ENST00000389840.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH17	ENST00000389840.7	c.8505C>T	p.Asp2835=	synonymous_variant	54/81	5	NM_173628.4	P1
DNAH17	ENST00000586052.5	n.1887C>T		non_coding_transcript_exon_variant	10/35	5

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17638 AN: 152132 Hom.: 1123 Cov.: 32

Gnomad AFR AF: 0.0867

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0993

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.119

GnomAD3 exomes AF: 0.130 AC: 32432 AN: 248784 Hom.: 2376 AF XY: 0.136 AC XY: 18321 AN XY: 135024

Gnomad AFR exome AF: 0.0835

Gnomad AMR exome AF: 0.0749

Gnomad ASJ exome AF: 0.106

Gnomad EAS exome AF: 0.195

Gnomad SAS exome AF: 0.187

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.135

GnomAD4 exome AF: 0.124 AC: 181214 AN: 1461562 Hom.: 11963 Cov.: 33 AF XY: 0.126 AC XY: 91705 AN XY: 727062

Gnomad4 AFR exome AF: 0.0821

Gnomad4 AMR exome AF: 0.0772

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.116 AC: 17660 AN: 152250 Hom.: 1129 Cov.: 32 AF XY: 0.119 AC XY: 8844 AN XY: 74456

Gnomad4 AFR AF: 0.0871

Gnomad4 AMR AF: 0.0990

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.122

Alfa AF: 0.117 Hom.: 513

Bravo AF: 0.108

Asia WGS AF: 0.201 AC: 700 AN: 3478

EpiCase AF: 0.124

EpiControl AF: 0.128

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 28, 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	-0.45
Cadd	Benign	8.6
Dann	Benign	0.91

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: rs61746438; hg19: chr17-76471366; COSMIC: COSV67754468; COSMIC: COSV67754468;