rs7570005

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.4611C>T(p.Ile1537Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0952 in 1,548,974 control chromosomes in the GnomAD database, including 12,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 4512 hom., cov: 32)

Exomes 𝑓: 0.086 ( 7726 hom. )

Consequence

DNAH6
NM_001370.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.92

Publications

8 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=-0.51).

BP6

Variant 2-84634599-C-T is Benign according to our data. Variant chr2-84634599-C-T is described in ClinVar as [Benign]. Clinvar id is 402737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH6	NM_001370.2 link	c.4611C>T	p.Ile1537Ile	synonymous_variant	Exon 30 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.4611C>T	p.Ile1537Ile	synonymous_variant	Exon 30 of 77	5	NM_001370.2	ENSP00000374045.3		Q9C0G6-1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27021

AN:

152094

Hom.:

4496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.437

Gnomad AMI

AF:

0.100

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.0605

Gnomad EAS

AF:

0.0133

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.0508

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.0778

Gnomad OTH

AF:

0.157

GnomAD2 exomes

AF:

0.0899

AC:

13865

AN:

154154

AF XY:

0.0873

show subpopulations

Gnomad AFR exome

AF:

0.440

Gnomad AMR exome

AF:

0.0688

Gnomad ASJ exome

AF:

0.0622

Gnomad EAS exome

AF:

0.00945

Gnomad FIN exome

AF:

0.0474

Gnomad NFE exome

AF:

0.0770

Gnomad OTH exome

AF:

0.0855

GnomAD4 exome

AF:

0.0861

AC:

120316

AN:

1396762

Hom.:

7726

Cov.:

AF XY:

0.0861

AC XY:

59299

AN XY:

688872

show subpopulations

African (AFR)

AF:

0.444

AC:

13894

AN:

31270

American (AMR)

AF:

0.0751

AC:

2657

AN:

35358

Ashkenazi Jewish (ASJ)

AF:

0.0621

AC:

1560

AN:

25116

East Asian (EAS)

AF:

0.0219

AC:

780

AN:

35550

South Asian (SAS)

AF:

0.109

AC:

8595

AN:

78746

European-Finnish (FIN)

AF:

0.0467

AC:

2301

AN:

49262

Middle Eastern (MID)

AF:

0.136

AC:

772

AN:

5686

European-Non Finnish (NFE)

AF:

0.0777

AC:

83699

AN:

1077862

Other (OTH)

AF:

0.105

AC:

6058

AN:

57912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

5259

10518

15777

21036

26295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.178

AC:

27083

AN:

152212

Hom.:

4512

Cov.:

AF XY:

0.174

AC XY:

12961

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.437

AC:

18145

AN:

41506

American (AMR)

AF:

0.119

AC:

1818

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0605

AC:

210

AN:

3472

East Asian (EAS)

AF:

0.0133

AC:

AN:

5184

South Asian (SAS)

AF:

0.110

AC:

532

AN:

4824

European-Finnish (FIN)

AF:

0.0508

AC:

539

AN:

10604

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0778

AC:

5294

AN:

68016

Other (OTH)

AF:

0.157

AC:

332

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

940

1881

2821

3762

4702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.122

Hom.:

1494

Bravo

AF:

0.192

Asia WGS

AF:

0.0890

AC:

309

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

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

Nov 25, 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

-0.51

CADD

Benign

1.2

(source)

DANN

Benign

0.69

PhyloP100

-3.9

Mutation Taster

=99/1

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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rs7570005

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