Variant rs754273 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_001370.2(DNAH6):c.11359+5A>G variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,498,844 control chromosomes in the GnomAD database, including 23,880 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4611 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19269 hom. )

Consequence

DNAH6
NM_001370.2 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.0002191

Clinical Significance

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

Conservation

PhyloP100: -0.310

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 2-84796430-A-G is Benign according to our data. Variant chr2-84796430-A-G is described in ClinVar as [Benign]. Clinvar id is 402745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH6	NM_001370.2 linkuse as main transcript	c.11359+5A>G		splice_donor_5th_base_variant, intron_variant		ENST00000389394.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH6	ENST00000389394.8 linkuse as main transcript	c.11359+5A>G		splice_donor_5th_base_variant, intron_variant		5	NM_001370.2	P1	Q9C0G6-1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34190

AN:

151944

Hom.:

4587

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.224

GnomAD3 exomes

AF:

0.174

AC:

22643

AN:

130108

Hom.:

2279

AF XY:

0.169

AC XY:

11648

AN XY:

68916

show subpopulations

Gnomad AFR exome

AF:

0.402

Gnomad AMR exome

AF:

0.211

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.102

Gnomad SAS exome

AF:

0.152

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.182

GnomAD4 exome

AF:

0.162

AC:

218027

AN:

1346782

Hom.:

19269

Cov.:

AF XY:

0.162

AC XY:

107328

AN XY:

662922

show subpopulations

Gnomad4 AFR exome

AF:

0.404

Gnomad4 AMR exome

AF:

0.205

Gnomad4 ASJ exome

AF:

0.180

Gnomad4 EAS exome

AF:

0.128

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.155

Gnomad4 OTH exome

AF:

0.172

GnomAD4 genome

AF:

0.225

AC:

34259

AN:

152062

Hom.:

4611

Cov.:

AF XY:

0.222

AC XY:

16545

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.395

Gnomad4 AMR

AF:

0.188

Gnomad4 ASJ

AF:

0.176

Gnomad4 EAS

AF:

0.106

Gnomad4 SAS

AF:

0.140

Gnomad4 FIN

AF:

0.157

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.172

Hom.:

2854

Bravo

AF:

0.236

Asia WGS

AF:

0.155

AC:

541

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 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, criteria provided, single submitter

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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.3

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00022

dbscSNV1_RF

Benign

0.062

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