NM_001206927.2:c.5769C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001206927.2(DNAH8):c.5769C>T(p.His1923His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,610,598 control chromosomes in the GnomAD database, including 156,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14154 hom., cov: 32)

Exomes 𝑓: 0.44 ( 142448 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.00900

Publications

14 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 6-38857553-C-T is Benign according to our data. Variant chr6-38857553-C-T is described in ClinVar as Benign. ClinVar VariationId is 402765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.009 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2 link	c.5769C>T	p.His1923His	synonymous_variant	Exon 42 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
DNAH8	ENST00000327475.11 link	c.5769C>T	p.His1923His	synonymous_variant	Exon 42 of 93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7 link	c.5118C>T	p.His1706His	synonymous_variant	Exon 40 of 91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6 link	c.5769C>T	p.His1923His	synonymous_variant	Exon 41 of 82	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

63975

AN:

151716

Hom.:

14113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.366

Gnomad AMI

AF:

0.443

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.693

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.413

GnomAD2 exomes

AF:

0.462

AC:

115703

AN:

250498

AF XY:

0.452

show subpopulations

Gnomad AFR exome

AF:

0.365

Gnomad AMR exome

AF:

0.625

Gnomad ASJ exome

AF:

0.360

Gnomad EAS exome

AF:

0.707

Gnomad FIN exome

AF:

0.372

Gnomad NFE exome

AF:

0.419

Gnomad OTH exome

AF:

0.416

GnomAD4 exome

AF:

0.437

AC:

637100

AN:

1458764

Hom.:

142448

Cov.:

AF XY:

0.435

AC XY:

315486

AN XY:

725748

show subpopulations

African (AFR)

AF:

0.355

AC:

11880

AN:

33424

American (AMR)

AF:

0.613

AC:

27361

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.359

AC:

9377

AN:

26114

East Asian (EAS)

AF:

0.689

AC:

27314

AN:

39624

South Asian (SAS)

AF:

0.441

AC:

38001

AN:

86076

European-Finnish (FIN)

AF:

0.374

AC:

19956

AN:

53392

Middle Eastern (MID)

AF:

0.353

AC:

2032

AN:

5762

European-Non Finnish (NFE)

AF:

0.428

AC:

474737

AN:

1109454

Other (OTH)

AF:

0.439

AC:

26442

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

15915

31830

47746

63661

79576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14712

29424

44136

58848

73560

<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:

0.422

AC:

64070

AN:

151834

Hom.:

14154

Cov.:

AF XY:

0.421

AC XY:

31251

AN XY:

74164

show subpopulations

African (AFR)

AF:

0.367

AC:

15182

AN:

41392

American (AMR)

AF:

0.523

AC:

7979

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

1231

AN:

3472

East Asian (EAS)

AF:

0.693

AC:

3584

AN:

5168

South Asian (SAS)

AF:

0.457

AC:

2193

AN:

4800

European-Finnish (FIN)

AF:

0.371

AC:

3905

AN:

10518

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.421

AC:

28591

AN:

67916

Other (OTH)

AF:

0.418

AC:

882

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1867

3735

5602

7470

9337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

598

1196

1794

2392

2990

<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:

0.413

Hom.:

19002

Bravo

AF:

0.431

Asia WGS

AF:

0.573

AC:

1992

AN:

3476

EpiCase

AF:

0.418

EpiControl

AF:

0.406

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

-0.38

CADD

Benign

2.5

(source)

DANN

Benign

0.40

PhyloP100

0.0090

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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