rs9380795

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001206927.2(DNAH8):c.7569G>A(p.Lys2523Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,611,190 control chromosomes in the GnomAD database, including 166,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15188 hom., cov: 32)

Exomes 𝑓: 0.45 ( 151651 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.264

Publications

12 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 6-38873325-G-A is Benign according to our data. Variant chr6-38873325-G-A is described in ClinVar as Benign. ClinVar VariationId is 402766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.264 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2 link	c.7569G>A	p.Lys2523Lys	synonymous_variant	Exon 52 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.7569G>A	p.Lys2523Lys	synonymous_variant	Exon 52 of 93	5	NM_001206927.2	ENSP00000333363.7	A0A075B6F3
DNAH8	ENST00000359357.7 link	c.6918G>A	p.Lys2306Lys	synonymous_variant	Exon 50 of 91	2		ENSP00000352312.3	Q96JB1-1
DNAH8	ENST00000449981.6 link	c.7569G>A	p.Lys2523Lys	synonymous_variant	Exon 51 of 82	5		ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

65708

AN:

151936

Hom.:

15151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.370

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.529

Gnomad ASJ

AF:

0.360

Gnomad EAS

AF:

0.841

Gnomad SAS

AF:

0.557

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.421

GnomAD2 exomes

AF:

0.486

AC:

120179

AN:

247394

AF XY:

0.479

show subpopulations

Gnomad AFR exome

AF:

0.368

Gnomad AMR exome

AF:

0.640

Gnomad ASJ exome

AF:

0.364

Gnomad EAS exome

AF:

0.847

Gnomad FIN exome

AF:

0.371

Gnomad NFE exome

AF:

0.420

Gnomad OTH exome

AF:

0.430

GnomAD4 exome

AF:

0.448

AC:

653463

AN:

1459136

Hom.:

151651

Cov.:

AF XY:

0.448

AC XY:

325236

AN XY:

725740

show subpopulations

African (AFR)

AF:

0.358

AC:

11939

AN:

33392

American (AMR)

AF:

0.626

AC:

27735

AN:

44274

Ashkenazi Jewish (ASJ)

AF:

0.363

AC:

9457

AN:

26040

East Asian (EAS)

AF:

0.821

AC:

32548

AN:

39646

South Asian (SAS)

AF:

0.529

AC:

45252

AN:

85484

European-Finnish (FIN)

AF:

0.375

AC:

19957

AN:

53288

Middle Eastern (MID)

AF:

0.365

AC:

2098

AN:

5748

European-Non Finnish (NFE)

AF:

0.429

AC:

476999

AN:

1110970

Other (OTH)

AF:

0.456

AC:

27478

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

17070

34140

51209

68279

85349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14842

29684

44526

59368

74210

<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:

0.433

AC:

65798

AN:

152054

Hom.:

15188

Cov.:

AF XY:

0.435

AC XY:

32310

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.370

AC:

15346

AN:

41464

American (AMR)

AF:

0.530

AC:

8097

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.360

AC:

1248

AN:

3468

East Asian (EAS)

AF:

0.841

AC:

4359

AN:

5184

South Asian (SAS)

AF:

0.556

AC:

2679

AN:

4818

European-Finnish (FIN)

AF:

0.371

AC:

3919

AN:

10554

Middle Eastern (MID)

AF:

0.412

AC:

121

AN:

294

European-Non Finnish (NFE)

AF:

0.423

AC:

28726

AN:

67978

Other (OTH)

AF:

0.427

AC:

899

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1825

3650

5476

7301

9126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

612

1224

1836

2448

3060

<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:

0.418

Hom.:

6870

Bravo

AF:

0.441

Asia WGS

AF:

0.678

AC:

2357

AN:

3478

EpiCase

AF:

0.420

EpiControl

AF:

0.409

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

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.49

(source)

DANN

Benign

0.45

PhyloP100

-0.26

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over