rs11868065

chr17-78532509-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.3087G>A(p.Pro1029=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,609,368 control chromosomes in the GnomAD database, including 217,936 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (19943 hom., cov: 31)
  • Exomes 𝑓: 0.52 (197993 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -6.21

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=-0.8).
• BP6: Variant 17-78532509-C-T is Benign according to our data. Variant chr17-78532509-C-T is described in ClinVar as [Benign]. Clinvar id is 402696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH17	NM_173628.4	c.3087G>A	p.Pro1029=	synonymous_variant	20/81	ENST00000389840.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH17	ENST00000389840.7	c.3087G>A	p.Pro1029=	synonymous_variant	20/81	5	NM_173628.4	P1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77319 AN: 151862 Hom.: 19934 Cov.: 31

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.521

GnomAD3 exomes AF: 0.492 AC: 119418 AN: 242860 Hom.: 29828 AF XY: 0.497 AC XY: 65527 AN XY: 131888

Gnomad AFR exome AF: 0.481

Gnomad AMR exome AF: 0.379

Gnomad ASJ exome AF: 0.531

Gnomad EAS exome AF: 0.430

Gnomad SAS exome AF: 0.441

Gnomad FIN exome AF: 0.519

Gnomad NFE exome AF: 0.542

Gnomad OTH exome AF: 0.517

GnomAD4 exome AF: 0.520 AC: 757622 AN: 1457388 Hom.: 197993 Cov.: 54 AF XY: 0.519 AC XY: 375851 AN XY: 724668

Gnomad4 AFR exome AF: 0.483

Gnomad4 AMR exome AF: 0.386

Gnomad4 ASJ exome AF: 0.530

Gnomad4 EAS exome AF: 0.440

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.524

Gnomad4 NFE exome AF: 0.534

Gnomad4 OTH exome AF: 0.518

GnomAD4 genome AF: 0.509 AC: 77360 AN: 151980 Hom.: 19943 Cov.: 31 AF XY: 0.505 AC XY: 37499 AN XY: 74262

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.518

Alfa AF: 0.530 Hom.: 10792

Bravo AF: 0.501

Asia WGS AF: 0.431 AC: 1499 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

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.063
Dann	Benign	0.74

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: rs11868065; hg19: chr17-76528591; COSMIC: COSV67755643; COSMIC: COSV67755643;