chr2-84670377-A-G

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.6356A>G(p.Tyr2119Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0241 in 1,543,308 control chromosomes in the GnomAD database, including 633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 50 hom., cov: 33)

Exomes 𝑓: 0.024 ( 583 hom. )

Consequence

DNAH6
NM_001370.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.57

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 (MetaRNN=0.0058374703).

BP6

Variant 2-84670377-A-G is Benign according to our data. Variant chr2-84670377-A-G is described in ClinVar as Benign. ClinVar VariationId is 402739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.054 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH6	NM_001370.2 link	c.6356A>G	p.Tyr2119Cys	missense_variant	Exon 39 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.6356A>G	p.Tyr2119Cys	missense_variant	Exon 39 of 77	5	NM_001370.2	ENSP00000374045.3		Q9C0G6-1
DNAH6	ENST00000602588.1 link	n.584A>G		non_coding_transcript_exon_variant	Exon 4 of 11	1

Frequencies

GnomAD3 genomes

AF:

0.0217

AC:

3303

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0361

Gnomad ASJ

AF:

0.0446

Gnomad EAS

AF:

0.0106

Gnomad SAS

AF:

0.0594

Gnomad FIN

AF:

0.0102

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0226

Gnomad OTH

AF:

0.0354

GnomAD2 exomes

AF:

0.0269

AC:

4126

AN:

153544

AF XY:

0.0294

show subpopulations

Gnomad AFR exome

AF:

0.0103

Gnomad AMR exome

AF:

0.0262

Gnomad ASJ exome

AF:

0.0469

Gnomad EAS exome

AF:

0.00805

Gnomad FIN exome

AF:

0.00975

Gnomad NFE exome

AF:

0.0234

Gnomad OTH exome

AF:

0.0321

GnomAD4 exome

AF:

0.0244

AC:

33895

AN:

1390978

Hom.:

583

Cov.:

AF XY:

0.0260

AC XY:

17841

AN XY:

686070

show subpopulations

African (AFR)

AF:

0.0116

AC:

364

AN:

31336

American (AMR)

AF:

0.0270

AC:

952

AN:

35196

Ashkenazi Jewish (ASJ)

AF:

0.0480

AC:

1204

AN:

25070

East Asian (EAS)

AF:

0.0207

AC:

736

AN:

35586

South Asian (SAS)

AF:

0.0609

AC:

4739

AN:

77800

European-Finnish (FIN)

AF:

0.00867

AC:

427

AN:

49264

Middle Eastern (MID)

AF:

0.0696

AC:

395

AN:

5672

European-Non Finnish (NFE)

AF:

0.0218

AC:

23405

AN:

1073314

Other (OTH)

AF:

0.0290

AC:

1673

AN:

57740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

1483

2966

4449

5932

7415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.0217

AC:

3305

AN:

152330

Hom.:

Cov.:

AF XY:

0.0223

AC XY:

1660

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0118

AC:

490

AN:

41574

American (AMR)

AF:

0.0361

AC:

552

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0446

AC:

155

AN:

3472

East Asian (EAS)

AF:

0.0106

AC:

AN:

5188

South Asian (SAS)

AF:

0.0597

AC:

288

AN:

4824

European-Finnish (FIN)

AF:

0.0102

AC:

108

AN:

10626

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0226

AC:

1537

AN:

68022

Other (OTH)

AF:

0.0364

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

166

333

499

666

832

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0234

Hom.:

155

Bravo

AF:

0.0218

TwinsUK

AF:

0.0232

AC:

ALSPAC

AF:

0.0195

AC:

ESP6500AA

AF:

0.00939

AC:

ESP6500EA

AF:

0.0236

AC:

ExAC

AF:

0.0338

AC:

827

Asia WGS

AF:

0.0390

AC:

134

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Jan 09, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29767709) -

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

T;T

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

D;.

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.9

M;M

PhyloP100

7.6

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-6.0

D;D

REVEL

Uncertain

0.49

Sift

Benign

0.031

D;D

Polyphen

1.0

D;D

Vest4

0.34

MPC

0.20

ClinPred

0.019

GERP RS

5.1

Varity_R

0.30

gMVP

0.78

Mutation Taster

=45/55

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