Variant 17-7802026-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020877.5(DNAH2):c.8972+9G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,613,706 control chromosomes in the GnomAD database, including 63,201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4382 hom., cov: 32)

Exomes 𝑓: 0.27 ( 58819 hom. )

Consequence

DNAH2
NM_020877.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.09

Variant links:

Genes affected

DNAH2 (HGNC:2948): (dynein axonemal heavy chain 2) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. The axonemal dyneins, found in cilia and flagella, are components of the outer and inner dynein arms attached to the peripheral microtubule doublets. DNAH2 is an axonemal inner arm dynein heavy chain (Chapelin et al., 1997 [PubMed 9256245]).[supplied by OMIM, Mar 2008]

DNAH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-7802026-G-C is Benign according to our data. Variant chr17-7802026-G-C is described in ClinVar as [Benign]. Clinvar id is 402711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH2	NM_020877.5 linkuse as main transcript	c.8972+9G>C		intron_variant		ENST00000572933.6	NP_065928.2	Q9P225-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH2	ENST00000572933.6 linkuse as main transcript	c.8972+9G>C		intron_variant		2	NM_020877.5	ENSP00000458355.1		Q9P225-1
DNAH2	ENST00000389173.6 linkuse as main transcript	c.8972+9G>C		intron_variant		2		ENSP00000373825.2		Q9P225-1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32653

AN:

152034

Hom.:

4384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0818

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.227

GnomAD3 exomes

AF:

0.224

AC:

56197

AN:

250980

Hom.:

7642

AF XY:

0.229

AC XY:

31021

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.0757

Gnomad AMR exome

AF:

0.145

Gnomad ASJ exome

AF:

0.289

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.295

Gnomad NFE exome

AF:

0.305

Gnomad OTH exome

AF:

0.270

GnomAD4 exome

AF:

0.273

AC:

399373

AN:

1461554

Hom.:

58819

Cov.:

AF XY:

0.271

AC XY:

197234

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.0758

Gnomad4 AMR exome

AF:

0.151

Gnomad4 ASJ exome

AF:

0.296

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.291

Gnomad4 NFE exome

AF:

0.303

Gnomad4 OTH exome

AF:

0.253

GnomAD4 genome

AF:

0.215

AC:

32640

AN:

152152

Hom.:

4382

Cov.:

AF XY:

0.210

AC XY:

15617

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0815

Gnomad4 AMR

AF:

0.197

Gnomad4 ASJ

AF:

0.290

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.143

Gnomad4 FIN

AF:

0.288

Gnomad4 NFE

AF:

0.304

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.178

Hom.:

530

Bravo

AF:

0.202

Asia WGS

AF:

0.0600

AC:

209

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

DNAH2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 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). -

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 -

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

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.010

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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