rs754273

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001370.2(DNAH6):c.11359+5A>G variant causes a splice region, 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_region, intron

Scores

Splicing: ADA: 0.0002191

Clinical Significance

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

Conservation

PhyloP100: -0.310

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

DNAH6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DNAH6	NM_001370.2 link	c.11359+5A>G		splice_region_variant, intron_variant	Intron 69 of 76	ENST00000389394.8	NP_001361.1	Q9C0G6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH6	ENST00000389394.8 link	c.11359+5A>G		splice_region_variant, intron_variant	Intron 69 of 76	5	NM_001370.2	ENSP00000374045.3		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

GnomAD2 exomes

AF:

0.174

AC:

22643

AN:

130108

AF XY:

0.169

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 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

African (AFR)

AF:

0.404

AC:

11779

AN:

29154

American (AMR)

AF:

0.205

AC:

5811

AN:

28296

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

4299

AN:

23828

East Asian (EAS)

AF:

0.128

AC:

4431

AN:

34752

South Asian (SAS)

AF:

0.148

AC:

10438

AN:

70574

European-Finnish (FIN)

AF:

0.152

AC:

7397

AN:

48540

Middle Eastern (MID)

AF:

0.215

AC:

1194

AN:

5544

European-Non Finnish (NFE)

AF:

0.155

AC:

163120

AN:

1050392

Other (OTH)

AF:

0.172

AC:

9558

AN:

55702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

6906

13812

20719

27625

34531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.225

AC:

34259

AN:

152062

Hom.:

4611

Cov.:

AF XY:

0.222

AC XY:

16545

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.395

AC:

16377

AN:

41440

American (AMR)

AF:

0.188

AC:

2870

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

611

AN:

3472

East Asian (EAS)

AF:

0.106

AC:

551

AN:

5178

South Asian (SAS)

AF:

0.140

AC:

673

AN:

4820

European-Finnish (FIN)

AF:

0.157

AC:

1659

AN:

10590

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.157

AC:

10664

AN:

67974

Other (OTH)

AF:

0.224

AC:

473

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1276

2553

3829

5106

6382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.180

Hom.:

8006

Bravo

AF:

0.236

Asia WGS

AF:

0.155

AC:

541

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

-0.79

CADD

Benign

8.3

(source)

DANN

Benign

0.53

PhyloP100

-0.31

Mutation Taster

=76/24

polymorphism (auto)

(source)

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

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rs754273

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over