rs113909197

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001206927.2(DNAH8):c.6856A>G(p.Ser2286Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,613,942 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 7 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 9.32

Publications

5 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052086562).

BP6

Variant 6-38870428-A-G is Benign according to our data. Variant chr6-38870428-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 407286.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00137 (209/152346) while in subpopulation AMR AF = 0.00379 (58/15306). AF 95% confidence interval is 0.00301. There are 1 homozygotes in GnomAd4. There are 90 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2 link	c.6856A>G	p.Ser2286Gly	missense_variant	Exon 49 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
DNAH8	ENST00000327475.11 link	c.6856A>G	p.Ser2286Gly	missense_variant	Exon 49 of 93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7 link	c.6205A>G	p.Ser2069Gly	missense_variant	Exon 47 of 91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6 link	c.6856A>G	p.Ser2286Gly	missense_variant	Exon 48 of 82	5		ENSP00000415331.2
DNAH8	ENST00000394393.3 link	c.340A>G	p.Ser114Gly	missense_variant	Exon 4 of 4	3		ENSP00000377916.3

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

209

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.00119

AC:

298

AN:

250902

AF XY:

0.00103

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000985

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00213

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00243

AC:

3551

AN:

1461596

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

1733

AN XY:

727078

show subpopulations

African (AFR)

AF:

0.000448

AC:

AN:

33472

American (AMR)

AF:

0.000783

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86216

European-Finnish (FIN)

AF:

0.000187

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00306

AC:

3404

AN:

1111844

Other (OTH)

AF:

0.00142

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

168

336

503

671

839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

264

396

528

660

<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:

0.00137

AC:

209

AN:

152346

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.000457

AC:

AN:

41578

American (AMR)

AF:

0.00379

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00190

AC:

129

AN:

68032

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00178

Hom.:

Bravo

AF:

0.00138

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00108

AC:

131

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00251

EpiControl

AF:

0.00255

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DNAH8-related disorder

Benign:1

May 15, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Primary ciliary dyskinesia

Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.037

MetaRNN

Benign

0.052

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

.;.;L

PhyloP100

9.3

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.9

.;D;D

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

.;D;D

Polyphen

1.0

.;.;D

Vest4

0.69

MVP

0.66

MPC

0.55

ClinPred

0.054

GERP RS

5.9

Varity_R

0.71

gMVP

0.56

Mutation Taster

=89/11

polymorphism

(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