NM_001206927.2:c.1549T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001206927.2(DNAH8):c.1549T>C(p.Tyr517His) variant causes a missense change. The variant allele was found at a frequency of 0.141 in 1,558,360 control chromosomes in the GnomAD database, including 17,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1386 hom., cov: 32)

Exomes 𝑓: 0.14 ( 16063 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.34

Publications

11 publications found

Variant links:

Genes affected

DNAH8 (HGNC:2952): (dynein axonemal heavy chain 8) The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules. [provided by RefSeq, Jan 2012]

DNAH8 Gene-Disease associations (from GenCC):

spermatogenic failure 46
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
spermatogenic failure 5
Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox
primary ciliary dyskinesia
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

DNAH8 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=0.002126515).

BP6

Variant 6-38761735-T-C is Benign according to our data. Variant chr6-38761735-T-C is described in ClinVar as Benign. ClinVar VariationId is 402760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2 link	c.1549T>C	p.Tyr517His	missense_variant	Exon 11 of 93	ENST00000327475.11	NP_001193856.1	Q96JB1Q8IU65A0A075B6F3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH8	ENST00000327475.11 link	c.1549T>C	p.Tyr517His	missense_variant	Exon 11 of 93	5	NM_001206927.2	ENSP00000333363.7	A0A075B6F3
DNAH8	ENST00000359357.7 link	c.898T>C	p.Tyr300His	missense_variant	Exon 9 of 91	2		ENSP00000352312.3	Q96JB1-1
DNAH8	ENST00000449981.6 link	c.1549T>C	p.Tyr517His	missense_variant	Exon 10 of 82	5		ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18497

AN:

152122

Hom.:

1376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0598

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.0154

Gnomad SAS

AF:

0.0510

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.153

Gnomad OTH

AF:

0.113

GnomAD2 exomes

AF:

0.130

AC:

27051

AN:

207336

AF XY:

0.125

show subpopulations

Gnomad AFR exome

AF:

0.0568

Gnomad AMR exome

AF:

0.268

Gnomad ASJ exome

AF:

0.109

Gnomad EAS exome

AF:

0.0106

Gnomad FIN exome

AF:

0.120

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.144

AC:

201814

AN:

1406120

Hom.:

16063

Cov.:

AF XY:

0.140

AC XY:

98181

AN XY:

699940

show subpopulations

African (AFR)

AF:

0.0564

AC:

1676

AN:

29716

American (AMR)

AF:

0.258

AC:

8799

AN:

34078

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

2736

AN:

24506

East Asian (EAS)

AF:

0.0157

AC:

560

AN:

35766

South Asian (SAS)

AF:

0.0530

AC:

4186

AN:

78948

European-Finnish (FIN)

AF:

0.123

AC:

6447

AN:

52474

Middle Eastern (MID)

AF:

0.0925

AC:

513

AN:

5544

European-Non Finnish (NFE)

AF:

0.156

AC:

169225

AN:

1087284

Other (OTH)

AF:

0.133

AC:

7672

AN:

57804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

7048

14096

21145

28193

35241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6026

12052

18078

24104

30130

<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:

0.122

AC:

18529

AN:

152240

Hom.:

1386

Cov.:

AF XY:

0.120

AC XY:

8929

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0598

AC:

2487

AN:

41556

American (AMR)

AF:

0.215

AC:

3288

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

371

AN:

3472

East Asian (EAS)

AF:

0.0154

AC:

AN:

5190

South Asian (SAS)

AF:

0.0506

AC:

244

AN:

4818

European-Finnish (FIN)

AF:

0.118

AC:

1252

AN:

10592

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.153

AC:

10435

AN:

68008

Other (OTH)

AF:

0.118

AC:

249

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

806

1612

2418

3224

4030

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<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:

0.142

Hom.:

5560

Bravo

AF:

0.127

TwinsUK

AF:

0.149

AC:

554

ALSPAC

AF:

0.162

AC:

623

ESP6500AA

AF:

0.0633

AC:

279

ESP6500EA

AF:

0.153

AC:

1313

ExAC

AF:

0.128

AC:

15513

Asia WGS

AF:

0.0770

AC:

270

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 -

Primary ciliary dyskinesia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

T;T;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.86

D;D;D

MetaRNN

Benign

0.0021

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.1

.;.;M

PhyloP100

4.3

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.8

.;D;D

REVEL

Benign

0.23

Sift

Benign

0.10

.;T;T

Polyphen

0.43

.;.;B

Vest4

0.30

MPC

0.44

ClinPred

0.029

GERP RS

6.0

Varity_R

0.49

gMVP

0.68

Mutation Taster

=93/7

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