Variant 2-84797607-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001370.2(DNAH6):c.11430C>T(p.Ile3810Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,550,648 control chromosomes in the GnomAD database, including 12,634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1160 hom., cov: 32)

Exomes 𝑓: 0.13 ( 11474 hom. )

Consequence

DNAH6
NM_001370.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.58

Variant links:

Genes affected

DNAH6 (HGNC:2951): (dynein axonemal heavy chain 6) This gene belongs to the dynein family, whose members encode large proteins that are constituents of the microtubule-associated motor protein complex. This complex is composed of dynein heavy, intermediate and light chains, which can be axonemal or cytoplasmic. This protein is an axonemal dynein heavy chain. It is involved in producing force for ciliary beating by using energy from ATP hydrolysis. Mutations in this gene may cause primary ciliary dyskinesia (PCD) as well as heterotaxy. [provided by RefSeq, Jun 2016]

DNAH6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 2-84797607-C-T is Benign according to our data. Variant chr2-84797607-C-T is described in ClinVar as [Benign]. Clinvar id is 402746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.58 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH6	NM_001370.2 linkuse as main transcript	c.11430C>T	p.Ile3810Ile	synonymous_variant	70/77	ENST00000389394.8	NP_001361.1	Q9C0G6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH6	ENST00000389394.8 linkuse as main transcript	c.11430C>T	p.Ile3810Ile	synonymous_variant	70/77	5	NM_001370.2	ENSP00000374045.3		Q9C0G6-1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18632

AN:

152050

Hom.:

1159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.328

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.0786

Gnomad SAS

AF:

0.0877

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.133

GnomAD3 exomes

AF:

0.124

AC:

19401

AN:

157092

Hom.:

1336

AF XY:

0.121

AC XY:

10042

AN XY:

83076

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.0772

Gnomad SAS exome

AF:

0.0944

Gnomad FIN exome

AF:

0.140

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.128

GnomAD4 exome

AF:

0.125

AC:

174910

AN:

1398480

Hom.:

11474

Cov.:

AF XY:

0.124

AC XY:

85741

AN XY:

689776

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.153

Gnomad4 EAS exome

AF:

0.0722

Gnomad4 SAS exome

AF:

0.0939

Gnomad4 FIN exome

AF:

0.142

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.122

AC:

18640

AN:

152168

Hom.:

1160

Cov.:

AF XY:

0.121

AC XY:

9020

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.115

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.0780

Gnomad4 SAS

AF:

0.0871

Gnomad4 FIN

AF:

0.144

Gnomad4 NFE

AF:

0.126

Gnomad4 OTH

AF:

0.132

Alfa

AF:

0.120

Hom.:

1620

Bravo

AF:

0.122

Asia WGS

AF:

0.0980

AC:

341

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 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 -

DNAH6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 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

BayesDel_noAF

Benign

-0.27

CADD

Benign

8.5

DANN

Benign

0.66

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