chr2-84528925-G-A

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.421G>A(p.Val141Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 1,549,342 control chromosomes in the GnomAD database, including 694,396 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 65940 hom., cov: 25)

Exomes 𝑓: 0.95 ( 628456 hom. )

Consequence

DNAH6
NM_001370.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.34

Publications

21 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=9.98577E-7).

BP6

Variant 2-84528925-G-A is Benign according to our data. Variant chr2-84528925-G-A is described in ClinVar as [Benign]. Clinvar id is 402731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH6	NM_001370.2 link	c.421G>A	p.Val141Met	missense_variant	Exon 4 of 77	ENST00000389394.8	NP_001361.1	Q9C0G6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH6	ENST00000389394.8 link	c.421G>A	p.Val141Met	missense_variant	Exon 4 of 77	5	NM_001370.2	ENSP00000374045.3	Q9C0G6-1
DNAH6	ENST00000494025.1 link	n.229+10874G>A		intron_variant	Intron 1 of 8	1
DNAH6	ENST00000468661.1 link	n.454+3187G>A		intron_variant	Intron 3 of 3	4
DNAH6	ENST00000476689.5 link	n.536+3187G>A		intron_variant	Intron 3 of 10	2

Frequencies

GnomAD3 genomes

AF:

0.933

AC:

140971

AN:

151042

Hom.:

65906

Cov.:

show subpopulations

Gnomad AFR

AF:

0.882

Gnomad AMI

AF:

0.916

Gnomad AMR

AF:

0.954

Gnomad ASJ

AF:

0.985

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.950

Gnomad FIN

AF:

0.960

Gnomad MID

AF:

0.956

Gnomad NFE

AF:

0.947

Gnomad OTH

AF:

0.946

GnomAD2 exomes

AF:

0.956

AC:

149258

AN:

156142

AF XY:

0.957

show subpopulations

Gnomad AFR exome

AF:

0.880

Gnomad AMR exome

AF:

0.972

Gnomad ASJ exome

AF:

0.985

Gnomad EAS exome

AF:

0.999

Gnomad FIN exome

AF:

0.962

Gnomad NFE exome

AF:

0.947

Gnomad OTH exome

AF:

0.959

GnomAD4 exome

AF:

0.948

AC:

1325338

AN:

1398186

Hom.:

628456

Cov.:

AF XY:

0.948

AC XY:

654069

AN XY:

689624

show subpopulations

African (AFR)

AF:

0.877

AC:

27655

AN:

31522

American (AMR)

AF:

0.971

AC:

34644

AN:

35670

Ashkenazi Jewish (ASJ)

AF:

0.986

AC:

24799

AN:

25150

East Asian (EAS)

AF:

0.999

AC:

35676

AN:

35710

South Asian (SAS)

AF:

0.952

AC:

75406

AN:

79178

European-Finnish (FIN)

AF:

0.962

AC:

47373

AN:

49254

Middle Eastern (MID)

AF:

0.958

AC:

5444

AN:

5682

European-Non Finnish (NFE)

AF:

0.946

AC:

1019415

AN:

1078078

Other (OTH)

AF:

0.948

AC:

54926

AN:

57942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

3319

6638

9956

13275

16594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.933

AC:

141059

AN:

151156

Hom.:

65940

Cov.:

AF XY:

0.935

AC XY:

68943

AN XY:

73772

show subpopulations

African (AFR)

AF:

0.882

AC:

36268

AN:

41126

American (AMR)

AF:

0.954

AC:

14475

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.985

AC:

3413

AN:

3466

East Asian (EAS)

AF:

0.997

AC:

5124

AN:

5138

South Asian (SAS)

AF:

0.950

AC:

4471

AN:

4708

European-Finnish (FIN)

AF:

0.960

AC:

9964

AN:

10384

Middle Eastern (MID)

AF:

0.952

AC:

280

AN:

294

European-Non Finnish (NFE)

AF:

0.947

AC:

64244

AN:

67856

Other (OTH)

AF:

0.946

AC:

1985

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

418

837

1255

1674

2092

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.945

Hom.:

197628

Bravo

AF:

0.932

TwinsUK

AF:

0.943

AC:

3497

ALSPAC

AF:

0.947

AC:

3651

ESP6500AA

AF:

0.872

AC:

1207

ESP6500EA

AF:

0.946

AC:

3010

ExAC

AF:

0.944

AC:

22356

Asia WGS

AF:

0.967

AC:

3362

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

Apr 17, 2019

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.034

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.0066

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0030

LIST_S2

Benign

0.45

T;.

MetaRNN

Benign

0.0000010

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.20

N;N

PhyloP100

-1.3

PrimateAI

Benign

0.28

PROVEAN

Benign

0.13

N;N

REVEL

Benign

0.0040

Sift

Benign

0.20

T;T

Polyphen

0.0010

B;B

Vest4

0.026

MPC

0.082

ClinPred

0.0030

GERP RS

-5.8

Varity_R

0.027

gMVP

0.14

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr2-84528925-G-A

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