rs2271613

chr17-78427016-G-A

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.12681C>T(p.Tyr4227=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 1,607,814 control chromosomes in the GnomAD database, including 423,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (34421 hom., cov: 32)
  • Exomes 𝑓: 0.73 (388778 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.423

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=-0.54).
• BP6: Variant 17-78427016-G-A is Benign according to our data. Variant chr17-78427016-G-A is described in ClinVar as [Benign]. Clinvar id is 402672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.423 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH17	NM_173628.4	c.12681C>T	p.Tyr4227=	synonymous_variant	78/81	ENST00000389840.7
DNAH17	XM_011525416.3	c.12693C>T	p.Tyr4231=	synonymous_variant	78/81
DNAH17	XM_024451013.2	c.12549C>T	p.Tyr4183=	synonymous_variant	77/80

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH17	ENST00000389840.7	c.12681C>T	p.Tyr4227=	synonymous_variant	78/81	5	NM_173628.4	P1

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99384 AN: 151968 Hom.: 34409 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.662

GnomAD3 exomes AF: 0.738 AC: 178120 AN: 241370 Hom.: 67146 AF XY: 0.737 AC XY: 96080 AN XY: 130402

Gnomad AFR exome AF: 0.408

Gnomad AMR exome AF: 0.816

Gnomad ASJ exome AF: 0.643

Gnomad EAS exome AF: 0.933

Gnomad SAS exome AF: 0.721

Gnomad FIN exome AF: 0.823

Gnomad NFE exome AF: 0.726

Gnomad OTH exome AF: 0.710

GnomAD4 exome AF: 0.727 AC: 1058665 AN: 1455728 Hom.: 388778 Cov.: 59 AF XY: 0.727 AC XY: 526203 AN XY: 723510

Gnomad4 AFR exome AF: 0.403

Gnomad4 AMR exome AF: 0.808

Gnomad4 ASJ exome AF: 0.640

Gnomad4 EAS exome AF: 0.950

Gnomad4 SAS exome AF: 0.720

Gnomad4 FIN exome AF: 0.821

Gnomad4 NFE exome AF: 0.725

Gnomad4 OTH exome AF: 0.717

GnomAD4 genome AF: 0.654 AC: 99423 AN: 152086 Hom.: 34421 Cov.: 32 AF XY: 0.663 AC XY: 49325 AN XY: 74350

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.937

Gnomad4 SAS AF: 0.732

Gnomad4 FIN AF: 0.831

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.663

Alfa AF: 0.709 Hom.: 88137

Bravo AF: 0.638

Asia WGS AF: 0.809 AC: 2809 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

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

Aug 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	1.1
Dann	Benign	0.93

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: rs2271613; hg19: chr17-76423097; COSMIC: COSV53145495; COSMIC: COSV53145495;