2-84517989-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001370.2(DNAH6):c.163C>T(p.His55Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00926 in 1,550,482 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H55N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0072 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0095 ( 71 hom. )

Consequence

DNAH6
NM_001370.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.53

Publications

6 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):

spermatogenic failure
Inheritance: AR Classification: STRONG Submitted by: ClinGen
male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center
primary ciliary dyskinesia
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

DNAH6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042708516).

BP6

Variant 2-84517989-C-T is Benign according to our data. Variant chr2-84517989-C-T is described in ClinVar as Benign. ClinVar VariationId is 782980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH6	NM_001370.2	MANE Select	c.163C>T	p.His55Tyr	missense	Exon 2 of 77	NP_001361.1	Q9C0G6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH6	ENST00000389394.8	TSL:5 MANE Select	c.163C>T	p.His55Tyr	missense	Exon 2 of 77	ENSP00000374045.3	Q9C0G6-1
DNAH6	ENST00000494025.1	TSL:1	n.167C>T		non_coding_transcript_exon	Exon 1 of 9
DNAH6	ENST00000468661.1	TSL:4	n.218C>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.00719

AC:

1093

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00864

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0108

Gnomad OTH

AF:

0.0101

GnomAD2 exomes

AF:

0.00649

AC:

1026

AN:

158184

AF XY:

0.00611

show subpopulations

Gnomad AFR exome

AF:

0.00133

Gnomad AMR exome

AF:

0.00599

Gnomad ASJ exome

AF:

0.00293

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00960

Gnomad NFE exome

AF:

0.0102

Gnomad OTH exome

AF:

0.00984

GnomAD4 exome

AF:

0.00949

AC:

13272

AN:

1398268

Hom.:

Cov.:

AF XY:

0.00907

AC XY:

6254

AN XY:

689678

show subpopulations

African (AFR)

AF:

0.00162

AC:

AN:

31548

American (AMR)

AF:

0.00740

AC:

264

AN:

35670

Ashkenazi Jewish (ASJ)

AF:

0.00283

AC:

AN:

25110

East Asian (EAS)

AF:

0.00

AC:

AN:

35588

South Asian (SAS)

AF:

0.000391

AC:

AN:

79192

European-Finnish (FIN)

AF:

0.00865

AC:

427

AN:

49338

Middle Eastern (MID)

AF:

0.00298

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.0110

AC:

11896

AN:

1078060

Other (OTH)

AF:

0.00887

AC:

515

AN:

58066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

694

1388

2081

2775

3469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.00718

AC:

1093

AN:

152214

Hom.:

Cov.:

AF XY:

0.00705

AC XY:

525

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00205

AC:

AN:

41548

American (AMR)

AF:

0.00863

AC:

132

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000208

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.0103

AC:

109

AN:

10602

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0108

AC:

734

AN:

67996

Other (OTH)

AF:

0.00996

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

107

160

214

267

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00883

Hom.:

Bravo

AF:

0.00701

TwinsUK

AF:

0.0105

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.00145

AC:

ESP6500EA

AF:

0.00974

AC:

ExAC

AF:

0.00452

AC:

114

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

DNAH6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0043

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

1.5

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.0

REVEL

Benign

0.051

Sift

Uncertain

0.0080

Polyphen

0.82

Vest4

0.31

MVP

0.27

MPC

0.14

ClinPred

0.031

GERP RS

4.6

Varity_R

0.11

gMVP

0.19

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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

Computational scores

Splicing

Publications

Other links and lift over