rs874808

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.3071G>A(p.Gly1024Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,602,908 control chromosomes in the GnomAD database, including 162,349 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13958 hom., cov: 32)

Exomes 𝑓: 0.45 ( 148391 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.12

Publications

22 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: ClinGen, Labcorp Genetics (formerly Invitae)
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=5.7039574E-6).

BP6

Variant 6-38805517-G-A is Benign according to our data. Variant chr6-38805517-G-A is described in ClinVar as Benign. ClinVar VariationId is 402762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206927.2. 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
	DNAH8	NM_001206927.2	MANE Select	c.3071G>A	p.Gly1024Glu	missense	Exon 23 of 93	NP_001193856.1	A0A075B6F3
	DNAH8	NM_001371.4		c.2420G>A	p.Gly807Glu	missense	Exon 22 of 92	NP_001362.2	Q96JB1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.3071G>A	p.Gly1024Glu	missense	Exon 23 of 93	ENSP00000333363.7	A0A075B6F3
DNAH8	ENST00000359357.7	TSL:2	c.2420G>A	p.Gly807Glu	missense	Exon 21 of 91	ENSP00000352312.3	Q96JB1-1
DNAH8	ENST00000449981.6	TSL:5	c.3071G>A	p.Gly1024Glu	missense	Exon 22 of 82	ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

63263

AN:

151900

Hom.:

13924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.539

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.697

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.432

Gnomad OTH

AF:

0.391

GnomAD2 exomes

AF:

0.467

AC:

117096

AN:

250718

AF XY:

0.458

show subpopulations

Gnomad AFR exome

AF:

0.334

Gnomad AMR exome

AF:

0.636

Gnomad ASJ exome

AF:

0.341

Gnomad EAS exome

AF:

0.717

Gnomad FIN exome

AF:

0.372

Gnomad NFE exome

AF:

0.432

Gnomad OTH exome

AF:

0.414

GnomAD4 exome

AF:

0.446

AC:

647553

AN:

1450890

Hom.:

148391

Cov.:

AF XY:

0.444

AC XY:

320871

AN XY:

722354

show subpopulations

African (AFR)

AF:

0.332

AC:

11029

AN:

33268

American (AMR)

AF:

0.623

AC:

27752

AN:

44548

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

8956

AN:

26056

East Asian (EAS)

AF:

0.698

AC:

27549

AN:

39486

South Asian (SAS)

AF:

0.444

AC:

38145

AN:

85958

European-Finnish (FIN)

AF:

0.377

AC:

20075

AN:

53270

Middle Eastern (MID)

AF:

0.351

AC:

2017

AN:

5744

European-Non Finnish (NFE)

AF:

0.441

AC:

485778

AN:

1102552

Other (OTH)

AF:

0.437

AC:

26252

AN:

60008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

15715

31430

47146

62861

78576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14868

29736

44604

59472

74340

<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:

0.417

AC:

63342

AN:

152018

Hom.:

13958

Cov.:

AF XY:

0.417

AC XY:

30960

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.333

AC:

13821

AN:

41470

American (AMR)

AF:

0.512

AC:

7825

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

1169

AN:

3466

East Asian (EAS)

AF:

0.698

AC:

3615

AN:

5180

South Asian (SAS)

AF:

0.460

AC:

2213

AN:

4816

European-Finnish (FIN)

AF:

0.372

AC:

3925

AN:

10552

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.432

AC:

29330

AN:

67934

Other (OTH)

AF:

0.396

AC:

838

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1785

3570

5354

7139

8924

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.429

Hom.:

49169

Bravo

AF:

0.426

TwinsUK

AF:

0.437

AC:

1621

ALSPAC

AF:

0.447

AC:

1723

ESP6500AA

AF:

0.339

AC:

1492

ESP6500EA

AF:

0.438

AC:

3768

ExAC

AF:

0.459

AC:

55666

Asia WGS

AF:

0.569

AC:

1978

AN:

3470

EpiCase

AF:

0.426

EpiControl

AF:

0.415

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.0065

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.11

MetaRNN

Benign

0.0000057

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.69

PhyloP100

2.1

PrimateAI

Benign

0.41

PROVEAN

Benign

1.1

REVEL

Benign

0.057

Sift

Benign

1.0

Polyphen

0.0

Vest4

0.064

MPC

0.16

ClinPred

0.0033

GERP RS

4.2

Varity_R

0.031

gMVP

0.16

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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