rs61758417

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.7171G>T(p.Ala2391Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,614,060 control chromosomes in the GnomAD database, including 909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 91 hom., cov: 33)

Exomes 𝑓: 0.011 ( 818 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 9.92

Publications

8 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=0.0022349358).

BP6

Variant 6-38872716-G-T is Benign according to our data. Variant chr6-38872716-G-T is described in CliVar as Benign. Clinvar id is 414424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-38872716-G-T is described in CliVar as Benign. Clinvar id is 414424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-38872716-G-T is described in CliVar as Benign. Clinvar id is 414424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-38872716-G-T is described in CliVar as Benign. Clinvar id is 414424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-38872716-G-T is described in CliVar as Benign. Clinvar id is 414424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2 link	c.7171G>T	p.Ala2391Ser	missense_variant	Exon 50 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.7171G>T	p.Ala2391Ser	missense_variant	Exon 50 of 93	5	NM_001206927.2	ENSP00000333363.7	A0A075B6F3
DNAH8	ENST00000359357.7 link	c.6520G>T	p.Ala2174Ser	missense_variant	Exon 48 of 91	2		ENSP00000352312.3	Q96JB1-1
DNAH8	ENST00000449981.6 link	c.7171G>T	p.Ala2391Ser	missense_variant	Exon 49 of 82	5		ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1576

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00727

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.0967

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00160

Gnomad OTH

AF:

0.00717

GnomAD2 exomes

AF:

0.0250

AC:

6272

AN:

251102

AF XY:

0.0280

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.0158

Gnomad ASJ exome

AF:

0.00437

Gnomad EAS exome

AF:

0.142

Gnomad FIN exome

AF:

0.000693

Gnomad NFE exome

AF:

0.00174

Gnomad OTH exome

AF:

0.0145

GnomAD4 exome

AF:

0.0112

AC:

16393

AN:

1461788

Hom.:

818

Cov.:

AF XY:

0.0136

AC XY:

9919

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

33470

American (AMR)

AF:

0.0143

AC:

639

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00448

AC:

117

AN:

26134

East Asian (EAS)

AF:

0.135

AC:

5338

AN:

39670

South Asian (SAS)

AF:

0.0888

AC:

7662

AN:

86258

European-Finnish (FIN)

AF:

0.000749

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.0135

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00132

AC:

1473

AN:

1111954

Other (OTH)

AF:

0.0167

AC:

1006

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

1003

2006

3010

4013

5016

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

226

452

678

904

1130

<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:

0.0103

AC:

1568

AN:

152272

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

948

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00204

AC:

AN:

41566

American (AMR)

AF:

0.00726

AC:

111

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3472

East Asian (EAS)

AF:

0.147

AC:

763

AN:

5176

South Asian (SAS)

AF:

0.0960

AC:

463

AN:

4824

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00160

AC:

109

AN:

68016

Other (OTH)

AF:

0.00710

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

154

230

307

384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00880

Hom.:

179

Bravo

AF:

0.00951

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.0257

AC:

3116

Asia WGS

AF:

0.104

AC:

359

AN:

3476

EpiCase

AF:

0.00267

EpiControl

AF:

0.00285

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

May 04, 2021

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

0.14

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

T;T;T

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

D;D;D

MetaRNN

Benign

0.0022

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

.;.;L

PhyloP100

9.9

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.6

.;D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.023

.;D;D

Polyphen

0.99

.;.;D

Vest4

0.48

MPC

0.47

ClinPred

0.026

GERP RS

5.6

Varity_R

0.35

gMVP

0.28

Mutation Taster

=96/4

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