Variant chr17-78484884-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_173628.4(DNAH17):c.7633A>G(p.Met2545Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,571,360 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0035 ( 7 hom., cov: 31)

Exomes 𝑓: 0.0022 ( 26 hom. )

Consequence

DNAH17
NM_173628.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.10

Variant links:

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 links:

DNAH17 (HGNC:):

DNAH17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0077292025).

BP6

Variant 17-78484884-T-C is Benign according to our data. Variant chr17-78484884-T-C is described in ClinVar as [Benign]. Clinvar id is 3045420.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00355 (540/152126) while in subpopulation EAS AF= 0.0147 (76/5158). AF 95% confidence interval is 0.0121. There are 7 homozygotes in gnomad4. There are 376 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH17	NM_173628.4 linkuse as main transcript	c.7633A>G	p.Met2545Val	missense_variant	48/81	ENST00000389840.7	NP_775899.3	Q9UFH2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7 linkuse as main transcript	c.7633A>G	p.Met2545Val	missense_variant	48/81	5	NM_173628.4	ENSP00000374490.6		Q9UFH2-1

Frequencies

GnomAD3 genomes

AF:

0.00355

AC:

540

AN:

152008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.0147

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.0328

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00100

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00518

AC:

948

AN:

182846

Hom.:

AF XY:

0.00475

AC XY:

467

AN XY:

98280

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000749

Gnomad ASJ exome

AF:

0.00927

Gnomad EAS exome

AF:

0.0150

Gnomad SAS exome

AF:

0.000687

Gnomad FIN exome

AF:

0.0300

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.00350

GnomAD4 exome

AF:

0.00217

AC:

3085

AN:

1419234

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

1483

AN XY:

702238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000926

Gnomad4 AMR exome

AF:

0.0000797

Gnomad4 ASJ exome

AF:

0.0105

Gnomad4 EAS exome

AF:

0.0142

Gnomad4 SAS exome

AF:

0.000801

Gnomad4 FIN exome

AF:

0.0297

Gnomad4 NFE exome

AF:

0.000469

Gnomad4 OTH exome

AF:

0.00345

GnomAD4 genome

AF:

0.00355

AC:

540

AN:

152126

Hom.:

Cov.:

AF XY:

0.00506

AC XY:

376

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.0147

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.0328

Gnomad4 NFE

AF:

0.00100

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00186

Hom.:

Bravo

AF:

0.00114

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000595

AC:

ExAC

AF:

0.00410

AC:

492

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DNAH17-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 21, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.97

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.89

D;T

MetaRNN

Benign

0.0077

T;T

MetaSVM

Benign

-0.89

PrimateAI

Uncertain

0.63

REVEL

Benign

0.12

Vest4

0.42

MVP

0.23

ClinPred

0.032

GERP RS

5.0

Varity_R

0.19

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over