rs1192295

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001370.2(DNAH6):c.7353A>G(p.Thr2451Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0621 in 1,552,234 control chromosomes in the GnomAD database, including 4,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1343 hom., cov: 33)

Exomes 𝑓: 0.058 ( 3152 hom. )

Consequence

DNAH6
NM_001370.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.139

Publications

7 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 2-84694309-A-G is Benign according to our data. Variant chr2-84694309-A-G is described in ClinVar as Benign. ClinVar VariationId is 402741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.139 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH6	NM_001370.2 link	c.7353A>G	p.Thr2451Thr	synonymous_variant	Exon 46 of 77	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.7353A>G	p.Thr2451Thr	synonymous_variant	Exon 46 of 77	5	NM_001370.2	ENSP00000374045.3		Q9C0G6-1
DNAH6	ENST00000602588.1 link	n.1434A>G		non_coding_transcript_exon_variant	Exon 10 of 11	1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15521

AN:

152206

Hom.:

1342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0593

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00211

Gnomad SAS

AF:

0.0610

Gnomad FIN

AF:

0.0409

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0556

Gnomad OTH

AF:

0.0812

GnomAD2 exomes

AF:

0.0553

AC:

8768

AN:

158578

AF XY:

0.0530

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.0343

Gnomad ASJ exome

AF:

0.0198

Gnomad EAS exome

AF:

0.00128

Gnomad FIN exome

AF:

0.0381

Gnomad NFE exome

AF:

0.0546

Gnomad OTH exome

AF:

0.0515

GnomAD4 exome

AF:

0.0578

AC:

80911

AN:

1399910

Hom.:

3152

Cov.:

AF XY:

0.0573

AC XY:

39574

AN XY:

690446

show subpopulations

African (AFR)

AF:

0.239

AC:

7539

AN:

31600

American (AMR)

AF:

0.0376

AC:

1342

AN:

35708

Ashkenazi Jewish (ASJ)

AF:

0.0192

AC:

484

AN:

25182

East Asian (EAS)

AF:

0.000811

AC:

AN:

35738

South Asian (SAS)

AF:

0.0644

AC:

5099

AN:

79234

European-Finnish (FIN)

AF:

0.0386

AC:

1913

AN:

49512

Middle Eastern (MID)

AF:

0.0614

AC:

350

AN:

5702

European-Non Finnish (NFE)

AF:

0.0560

AC:

60447

AN:

1079064

Other (OTH)

AF:

0.0637

AC:

3708

AN:

58170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

4316

8633

12949

17266

21582

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2396

4792

7188

9584

11980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.102

AC:

15544

AN:

152324

Hom.:

1343

Cov.:

AF XY:

0.0994

AC XY:

7401

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.235

AC:

9779

AN:

41552

American (AMR)

AF:

0.0592

AC:

906

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

AN:

3472

East Asian (EAS)

AF:

0.00212

AC:

AN:

5192

South Asian (SAS)

AF:

0.0613

AC:

296

AN:

4830

European-Finnish (FIN)

AF:

0.0409

AC:

434

AN:

10624

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0556

AC:

3783

AN:

68030

Other (OTH)

AF:

0.0803

AC:

170

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

699

1398

2097

2796

3495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0692

Hom.:

2152

Bravo

AF:

0.107

Asia WGS

AF:

0.0460

AC:

162

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: MAF -

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

-0.61

CADD

Benign

3.1

(source)

DANN

Benign

0.66

PhyloP100

-0.14

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

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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