rs61748601

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.1975G>A(p.Ala659Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,550,288 control chromosomes in the GnomAD database, including 16,848 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1395 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15453 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.719

Publications

9 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=0.0015652776).

BP6

Variant 6-38778400-G-A is Benign according to our data. Variant chr6-38778400-G-A is described in ClinVar as Benign. ClinVar VariationId is 402761.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.

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.1975G>A	p.Ala659Thr	missense	Exon 14 of 93	NP_001193856.1	A0A075B6F3
	DNAH8	NM_001371.4		c.1324G>A	p.Ala442Thr	missense	Exon 13 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.1975G>A	p.Ala659Thr	missense	Exon 14 of 93	ENSP00000333363.7	A0A075B6F3
DNAH8	ENST00000359357.7	TSL:2	c.1324G>A	p.Ala442Thr	missense	Exon 12 of 91	ENSP00000352312.3	Q96JB1-1
DNAH8	ENST00000449981.6	TSL:5	c.1975G>A	p.Ala659Thr	missense	Exon 13 of 82	ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18608

AN:

152002

Hom.:

1385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0624

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.0154

Gnomad SAS

AF:

0.0515

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.153

Gnomad OTH

AF:

0.114

GnomAD2 exomes

AF:

0.134

AC:

32702

AN:

243978

AF XY:

0.128

show subpopulations

Gnomad AFR exome

AF:

0.0607

Gnomad AMR exome

AF:

0.274

Gnomad ASJ exome

AF:

0.110

Gnomad EAS exome

AF:

0.0107

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.149

Gnomad OTH exome

AF:

0.137

GnomAD4 exome

AF:

0.140

AC:

195835

AN:

1398168

Hom.:

15453

Cov.:

AF XY:

0.137

AC XY:

95682

AN XY:

698356

show subpopulations

African (AFR)

AF:

0.0590

AC:

1894

AN:

32108

American (AMR)

AF:

0.264

AC:

11297

AN:

42752

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

2826

AN:

25502

East Asian (EAS)

AF:

0.0153

AC:

596

AN:

39076

South Asian (SAS)

AF:

0.0522

AC:

4304

AN:

82442

European-Finnish (FIN)

AF:

0.125

AC:

6599

AN:

52946

Middle Eastern (MID)

AF:

0.0942

AC:

515

AN:

5468

European-Non Finnish (NFE)

AF:

0.151

AC:

160180

AN:

1059748

Other (OTH)

AF:

0.131

AC:

7624

AN:

58126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

6523

13047

19570

26094

32617

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5532

11064

16596

22128

27660

<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:

0.123

AC:

18652

AN:

152120

Hom.:

1395

Cov.:

AF XY:

0.121

AC XY:

8986

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0629

AC:

2609

AN:

41506

American (AMR)

AF:

0.216

AC:

3296

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

371

AN:

3470

East Asian (EAS)

AF:

0.0154

AC:

AN:

5186

South Asian (SAS)

AF:

0.0507

AC:

244

AN:

4816

European-Finnish (FIN)

AF:

0.119

AC:

1260

AN:

10564

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.153

AC:

10420

AN:

67974

Other (OTH)

AF:

0.118

AC:

249

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

844

1688

2533

3377

4221

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:

0.136

Hom.:

3826

Bravo

AF:

0.128

TwinsUK

AF:

0.149

AC:

553

ALSPAC

AF:

0.161

AC:

620

ESP6500AA

AF:

0.0651

AC:

287

ESP6500EA

AF:

0.152

AC:

1305

ExAC

AF:

0.128

AC:

15532

Asia WGS

AF:

0.0790

AC:

277

AN:

3478

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

0.067

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.0077

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.18

PhyloP100

0.72

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.48

REVEL

Benign

0.093

Sift

Benign

0.71

Polyphen

0.0

Vest4

0.094

MPC

0.12

ClinPred

0.0011

GERP RS

3.5

Varity_R

0.051

gMVP

0.14

Mutation Taster

=99/1

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

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