2-84588891-A-G

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.2547A>G(p.Gln849Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0404 in 1,550,324 control chromosomes in the GnomAD database, including 3,985 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1846 hom., cov: 32)

Exomes 𝑓: 0.034 ( 2139 hom. )

Consequence

DNAH6
NM_001370.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.318

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 2-84588891-A-G is Benign according to our data. Variant chr2-84588891-A-G is described in ClinVar as [Benign]. Clinvar id is 402735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.318 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH6	NM_001370.2 link	c.2547A>G	p.Gln849Gln	synonymous_variant	Exon 16 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.2547A>G	p.Gln849Gln	synonymous_variant	Exon 16 of 77	5	NM_001370.2	ENSP00000374045.3		Q9C0G6-1

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15688

AN:

152144

Hom.:

1845

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0686

Gnomad ASJ

AF:

0.0481

Gnomad EAS

AF:

0.0114

Gnomad SAS

AF:

0.0602

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0248

Gnomad OTH

AF:

0.0985

GnomAD2 exomes

AF:

0.0456

AC:

7154

AN:

156774

AF XY:

0.0443

show subpopulations

Gnomad AFR exome

AF:

0.293

Gnomad AMR exome

AF:

0.0399

Gnomad ASJ exome

AF:

0.0524

Gnomad EAS exome

AF:

0.00937

Gnomad FIN exome

AF:

0.00977

Gnomad NFE exome

AF:

0.0257

Gnomad OTH exome

AF:

0.0424

GnomAD4 exome

AF:

0.0335

AC:

46890

AN:

1398062

Hom.:

2139

Cov.:

AF XY:

0.0341

AC XY:

23542

AN XY:

689544

show subpopulations

African (AFR)

AF:

0.293

AC:

9214

AN:

31460

American (AMR)

AF:

0.0440

AC:

1563

AN:

35562

Ashkenazi Jewish (ASJ)

AF:

0.0518

AC:

1301

AN:

25120

East Asian (EAS)

AF:

0.0210

AC:

746

AN:

35592

South Asian (SAS)

AF:

0.0626

AC:

4942

AN:

78998

European-Finnish (FIN)

AF:

0.00859

AC:

424

AN:

49348

Middle Eastern (MID)

AF:

0.0874

AC:

497

AN:

5688

European-Non Finnish (NFE)

AF:

0.0235

AC:

25289

AN:

1078292

Other (OTH)

AF:

0.0502

AC:

2914

AN:

58002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

1968

3936

5905

7873

9841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.103

AC:

15705

AN:

152262

Hom.:

1846

Cov.:

AF XY:

0.0998

AC XY:

7431

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.291

AC:

12088

AN:

41526

American (AMR)

AF:

0.0685

AC:

1048

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0481

AC:

167

AN:

3470

East Asian (EAS)

AF:

0.0114

AC:

AN:

5186

South Asian (SAS)

AF:

0.0601

AC:

290

AN:

4828

European-Finnish (FIN)

AF:

0.0103

AC:

109

AN:

10618

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0248

AC:

1685

AN:

68024

Other (OTH)

AF:

0.0989

AC:

209

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

602

1204

1805

2407

3009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0607

Hom.:

541

Bravo

AF:

0.114

Asia WGS

AF:

0.0540

AC:

188

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

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

-0.94

CADD

Benign

0.18

(source)

DANN

Benign

0.16

PhyloP100

-0.32

Mutation Taster

=100/0

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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2-84588891-A-G

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