Variant 17-7727187-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020877.5(DNAH2):c.294T>C(p.His98=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,607,788 control chromosomes in the GnomAD database, including 20,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1646 hom., cov: 31)

Exomes 𝑓: 0.16 ( 19111 hom. )

Consequence

DNAH2
NM_020877.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.15

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 17-7727187-T-C is Benign according to our data. Variant chr17-7727187-T-C is described in ClinVar as [Benign]. Clinvar id is 402705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 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.294T>C	p.His98=	synonymous_variant	4/86	ENST00000572933.6	NP_065928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH2	ENST00000572933.6 linkuse as main transcript	c.294T>C	p.His98=	synonymous_variant	4/86	2	NM_020877.5	ENSP00000458355	P1	Q9P225-1
DNAH2	ENST00000570791.5 linkuse as main transcript	c.294T>C	p.His98=	synonymous_variant	4/14	1		ENSP00000460245		Q9P225-3
DNAH2	ENST00000389173.6 linkuse as main transcript	c.294T>C	p.His98=	synonymous_variant	3/85	2		ENSP00000373825	P1	Q9P225-1

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21064

AN:

152050

Hom.:

1642

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.300

Gnomad AMR

AF:

0.0924

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.0922

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.127

AC:

31251

AN:

245628

Hom.:

2358

AF XY:

0.129

AC XY:

17161

AN XY:

133232

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.0566

Gnomad ASJ exome

AF:

0.152

Gnomad EAS exome

AF:

0.000279

Gnomad SAS exome

AF:

0.0874

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.170

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.157

AC:

228567

AN:

1455620

Hom.:

19111

Cov.:

AF XY:

0.155

AC XY:

112073

AN XY:

724248

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.0613

Gnomad4 ASJ exome

AF:

0.155

Gnomad4 EAS exome

AF:

0.000381

Gnomad4 SAS exome

AF:

0.0882

Gnomad4 FIN exome

AF:

0.173

Gnomad4 NFE exome

AF:

0.173

Gnomad4 OTH exome

AF:

0.145

GnomAD4 genome

AF:

0.139

AC:

21089

AN:

152168

Hom.:

1646

Cov.:

AF XY:

0.136

AC XY:

10109

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.0923

Gnomad4 ASJ

AF:

0.153

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0933

Gnomad4 FIN

AF:

0.170

Gnomad4 NFE

AF:

0.169

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.157

Hom.:

3294

Bravo

AF:

0.132

Asia WGS

AF:

0.0490

AC:

171

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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: MAF -

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 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

-0.93

CADD

Benign

0.078

DANN

Benign

0.39

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

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