17-78502610-C-T

Position:

• chr17-78502610-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173628.4(DNAH17):​c.5171G>A​(p.Arg1724Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 1,612,524 control chromosomes in the GnomAD database, including 568,007 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (58178 hom., cov: 32)
  • Exomes 𝑓: 0.83 (509829 hom.)
• Consequence: DNAH17 NM_173628.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.91

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.9313097E-7).
• BP6: Variant 17-78502610-C-T is Benign according to our data. Variant chr17-78502610-C-T is described in ClinVar as [Benign]. Clinvar id is 402687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.5171G>A	p.Arg1724Lys	missense_variant	33/81	ENST00000389840.7	NP_775899.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.5171G>A	p.Arg1724Lys	missense_variant	33/81	5	NM_173628.4	ENSP00000374490.6
DNAH17-AS1	ENST00000598378.2	n.4151C>T		non_coding_transcript_exon_variant	2/2	2
DNAH17	ENST00000587177.1	n.1135-73G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132484 AN: 152158 Hom.: 58116 Cov.: 32

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.877

GnomAD3 exomes AF: 0.865 AC: 213738 AN: 247090 Hom.: 93062 AF XY: 0.862 AC XY: 115610 AN XY: 134096

Gnomad AFR exome AF: 0.972

Gnomad AMR exome AF: 0.919

Gnomad ASJ exome AF: 0.870

Gnomad EAS exome AF: 0.977

Gnomad SAS exome AF: 0.927

Gnomad FIN exome AF: 0.810

Gnomad NFE exome AF: 0.810

Gnomad OTH exome AF: 0.848

GnomAD4 exome AF: 0.834 AC: 1218005 AN: 1460248 Hom.: 509829 Cov.: 47 AF XY: 0.835 AC XY: 606759 AN XY: 726394

Gnomad4 AFR exome AF: 0.975

Gnomad4 AMR exome AF: 0.915

Gnomad4 ASJ exome AF: 0.870

Gnomad4 EAS exome AF: 0.988

Gnomad4 SAS exome AF: 0.925

Gnomad4 FIN exome AF: 0.811

Gnomad4 NFE exome AF: 0.813

Gnomad4 OTH exome AF: 0.853

GnomAD4 genome AF: 0.871 AC: 132605 AN: 152276 Hom.: 58178 Cov.: 32 AF XY: 0.873 AC XY: 65030 AN XY: 74460

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.978

Gnomad4 SAS AF: 0.932

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.879

Alfa AF: 0.830 Hom.: 69688

Bravo AF: 0.881

TwinsUK AF: 0.817 AC: 3029

ALSPAC AF: 0.814 AC: 3139

ESP6500AA AF: 0.971 AC: 3895

ESP6500EA AF: 0.812 AC: 6854

ExAC AF: 0.864 AC: 104442

Asia WGS AF: 0.965 AC: 3357 AN: 3478

EpiCase AF: 0.809

EpiControl AF: 0.814

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, no assertion criteria provided

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

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Benign	0.46
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.58	T;T
MetaRNN	Benign	6.9e-7	T;T
MetaSVM	Benign	-0.93	T
PrimateAI	Uncertain	0.49	T
REVEL	Benign	0.054
Vest4		0.024
ClinPred		0.010	T
GERP RS		3.3
Varity_R		0.060
gMVP		0.22

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: rs930571; hg19: chr17-76498692;