2-84544443-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001370.2(DNAH6):c.873C>T(p.Ser291Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,528,912 control chromosomes in the GnomAD database, including 640,892 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 53456 hom., cov: 32)

Exomes 𝑓: 0.92 ( 587436 hom. )

Consequence

DNAH6
NM_001370.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.457

Publications

12 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 2-84544443-C-T is Benign according to our data. Variant chr2-84544443-C-T is described in ClinVar as Benign. ClinVar VariationId is 402733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.457 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH6	NM_001370.2	MANE Select	c.873C>T	p.Ser291Ser	synonymous	Exon 5 of 77	NP_001361.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAH6	ENST00000389394.8	TSL:5 MANE Select	c.873C>T	p.Ser291Ser	synonymous	Exon 5 of 77	ENSP00000374045.3
DNAH6	ENST00000494025.1	TSL:1	n.230-3845C>T		intron	N/A
DNAH6	ENST00000476689.5	TSL:2	n.537-3845C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.818

AC:

124372

AN:

151980

Hom.:

53448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.526

Gnomad AMI

AF:

0.902

Gnomad AMR

AF:

0.890

Gnomad ASJ

AF:

0.936

Gnomad EAS

AF:

0.987

Gnomad SAS

AF:

0.890

Gnomad FIN

AF:

0.955

Gnomad MID

AF:

0.832

Gnomad NFE

AF:

0.933

Gnomad OTH

AF:

0.847

GnomAD2 exomes

AF:

0.911

AC:

140725

AN:

154432

AF XY:

0.914

show subpopulations

Gnomad AFR exome

AF:

0.509

Gnomad AMR exome

AF:

0.937

Gnomad ASJ exome

AF:

0.932

Gnomad EAS exome

AF:

0.989

Gnomad FIN exome

AF:

0.957

Gnomad NFE exome

AF:

0.932

Gnomad OTH exome

AF:

0.920

GnomAD4 exome

AF:

0.921

AC:

1268318

AN:

1376814

Hom.:

587436

Cov.:

AF XY:

0.921

AC XY:

626734

AN XY:

680216

show subpopulations

African (AFR)

AF:

0.510

AC:

15949

AN:

31260

American (AMR)

AF:

0.931

AC:

33212

AN:

35660

Ashkenazi Jewish (ASJ)

AF:

0.934

AC:

23330

AN:

24988

East Asian (EAS)

AF:

0.978

AC:

34709

AN:

35484

South Asian (SAS)

AF:

0.890

AC:

69943

AN:

78590

European-Finnish (FIN)

AF:

0.957

AC:

47020

AN:

49140

Middle Eastern (MID)

AF:

0.869

AC:

4912

AN:

5654

European-Non Finnish (NFE)

AF:

0.933

AC:

987710

AN:

1058806

Other (OTH)

AF:

0.900

AC:

51533

AN:

57232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

3992

7984

11976

15968

19960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20624

41248

61872

82496

103120

<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:

0.818

AC:

124418

AN:

152098

Hom.:

53456

Cov.:

AF XY:

0.822

AC XY:

61129

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.526

AC:

21782

AN:

41446

American (AMR)

AF:

0.891

AC:

13604

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.936

AC:

3250

AN:

3472

East Asian (EAS)

AF:

0.986

AC:

5110

AN:

5180

South Asian (SAS)

AF:

0.890

AC:

4293

AN:

4824

European-Finnish (FIN)

AF:

0.955

AC:

10133

AN:

10606

Middle Eastern (MID)

AF:

0.823

AC:

242

AN:

294

European-Non Finnish (NFE)

AF:

0.933

AC:

63391

AN:

67976

Other (OTH)

AF:

0.848

AC:

1790

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

900

1799

2699

3598

4498

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

860

1720

2580

3440

4300

<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:

0.874

Hom.:

27178

Bravo

AF:

0.803

Asia WGS

AF:

0.908

AC:

3150

AN:

3468

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

Nov 01, 2018

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

0.46

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over