Variant rs7359662 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.5265C>G(p.Val1755=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 1,613,820 control chromosomes in the GnomAD database, including 672,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 52302 hom., cov: 31)

Exomes 𝑓: 0.92 ( 620501 hom. )

Consequence

DNAH2
NM_020877.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0290

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=-0.56).

BP6

Variant 17-7778094-C-G is Benign according to our data. Variant chr17-7778094-C-G is described in ClinVar as [Benign]. Clinvar id is 402709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.029 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.934 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.5265C>G	p.Val1755=	synonymous_variant	34/86	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.5265C>G	p.Val1755=	synonymous_variant	34/86	2	NM_020877.5	ENSP00000458355	P1	Q9P225-1
DNAH2	ENST00000389173.6 linkuse as main transcript	c.5265C>G	p.Val1755=	synonymous_variant	33/85	2		ENSP00000373825	P1	Q9P225-1
DNAH2	ENST00000574518.1 linkuse as main transcript	c.*1641C>G		3_prime_UTR_variant, NMD_transcript_variant	15/22	2		ENSP00000461273

Frequencies

GnomAD3 genomes

AF:

0.806

AC:

122591

AN:

152006

Hom.:

52282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.505

Gnomad AMI

AF:

0.922

Gnomad AMR

AF:

0.861

Gnomad ASJ

AF:

0.905

Gnomad EAS

AF:

0.807

Gnomad SAS

AF:

0.872

Gnomad FIN

AF:

0.971

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.940

Gnomad OTH

AF:

0.820

GnomAD3 exomes

AF:

0.881

AC:

221642

AN:

251442

Hom.:

99324

AF XY:

0.888

AC XY:

120722

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.871

Gnomad ASJ exome

AF:

0.907

Gnomad EAS exome

AF:

0.801

Gnomad SAS exome

AF:

0.866

Gnomad FIN exome

AF:

0.967

Gnomad NFE exome

AF:

0.937

Gnomad OTH exome

AF:

0.903

GnomAD4 exome

AF:

0.918

AC:

1342151

AN:

1461696

Hom.:

620501

Cov.:

AF XY:

0.918

AC XY:

667388

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.492

Gnomad4 AMR exome

AF:

0.872

Gnomad4 ASJ exome

AF:

0.909

Gnomad4 EAS exome

AF:

0.798

Gnomad4 SAS exome

AF:

0.865

Gnomad4 FIN exome

AF:

0.967

Gnomad4 NFE exome

AF:

0.941

Gnomad4 OTH exome

AF:

0.892

GnomAD4 genome

AF:

0.806

AC:

122657

AN:

152124

Hom.:

52302

Cov.:

AF XY:

0.811

AC XY:

60306

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.506

Gnomad4 AMR

AF:

0.861

Gnomad4 ASJ

AF:

0.905

Gnomad4 EAS

AF:

0.806

Gnomad4 SAS

AF:

0.871

Gnomad4 FIN

AF:

0.971

Gnomad4 NFE

AF:

0.940

Gnomad4 OTH

AF:

0.822

Alfa

AF:

0.898

Hom.:

20250

Bravo

AF:

0.785

Asia WGS

AF:

0.849

AC:

2952

AN:

3478

EpiCase

AF:

0.935

EpiControl

AF:

0.929

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: Frequency -

DNAH2-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

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.9

DANN

Benign

0.61

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