rs3209030

chr17-78427070-C-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.12627G>A(p.Pro4209=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 1,591,330 control chromosomes in the GnomAD database, including 7,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.087 (623 hom., cov: 32)
  • Exomes 𝑓: 0.091 (6379 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.51

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 17-78427070-C-T is Benign according to our data. Variant chr17-78427070-C-T is described in ClinVar as [Benign]. Clinvar id is 402673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH17	NM_173628.4	c.12627G>A	p.Pro4209=	synonymous_variant	78/81	ENST00000389840.7
DNAH17	XM_011525416.3	c.12639G>A	p.Pro4213=	synonymous_variant	78/81
DNAH17	XM_024451013.2	c.12495G>A	p.Pro4165=	synonymous_variant	77/80

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH17	ENST00000389840.7	c.12627G>A	p.Pro4209=	synonymous_variant	78/81	5	NM_173628.4	P1

Frequencies

GnomAD3 genomes AF: 0.0872 AC: 13257 AN: 152094 Hom.: 622 Cov.: 32

Gnomad AFR AF: 0.0936

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0691

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0313

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0424

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0960

Gnomad OTH AF: 0.0919

GnomAD3 exomes AF: 0.0822 AC: 17452 AN: 212394 Hom.: 832 AF XY: 0.0853 AC XY: 9746 AN XY: 114222

Gnomad AFR exome AF: 0.0890

Gnomad AMR exome AF: 0.0509

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.0317

Gnomad SAS exome AF: 0.115

Gnomad FIN exome AF: 0.0474

Gnomad NFE exome AF: 0.0931

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.0912 AC: 131261 AN: 1439118 Hom.: 6379 Cov.: 36 AF XY: 0.0926 AC XY: 66122 AN XY: 713684

Gnomad4 AFR exome AF: 0.0947

Gnomad4 AMR exome AF: 0.0535

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.0282

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.0483

Gnomad4 NFE exome AF: 0.0941

Gnomad4 OTH exome AF: 0.0940

GnomAD4 genome AF: 0.0871 AC: 13263 AN: 152212 Hom.: 623 Cov.: 32 AF XY: 0.0850 AC XY: 6322 AN XY: 74412

Gnomad4 AFR AF: 0.0935

Gnomad4 AMR AF: 0.0691

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.0314

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0424

Gnomad4 NFE AF: 0.0960

Gnomad4 OTH AF: 0.0914

Alfa AF: 0.0939 Hom.: 372

Bravo AF: 0.0869

Asia WGS AF: 0.0790 AC: 279 AN: 3478

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

Nov 20, 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

Aug 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	2.9
Dann	Benign	0.90

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: rs3209030; hg19: chr17-76423151; COSMIC: COSV53145967; COSMIC: COSV53145967;