6-38883977-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001206927.2(DNAH8):c.8238G>C(p.Val2746Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000527 in 1,571,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 0 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0140

Publications

1 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 6-38883977-G-C is Benign according to our data. Variant chr6-38883977-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 525461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.014 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	NM_001206927.2	MANE Select	c.8238G>C	p.Val2746Val	synonymous	Exon 56 of 93	NP_001193856.1
	DNAH8	NM_001371.4		c.7587G>C	p.Val2529Val	synonymous	Exon 55 of 92	NP_001362.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.8238G>C	p.Val2746Val	synonymous	Exon 56 of 93	ENSP00000333363.7
DNAH8	ENST00000359357.7	TSL:2	c.7587G>C	p.Val2529Val	synonymous	Exon 54 of 91	ENSP00000352312.3
DNAH8	ENST00000449981.6	TSL:5	c.8238G>C	p.Val2746Val	synonymous	Exon 55 of 82	ENSP00000415331.2

Frequencies

GnomAD3 genomes

AF:

0.000382

AC:

AN:

151956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000244

AC:

AN:

237292

AF XY:

0.000279

show subpopulations

Gnomad AFR exome

AF:

0.0000664

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000527

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000543

AC:

771

AN:

1419598

Hom.:

Cov.:

AF XY:

0.000496

AC XY:

350

AN XY:

705414

show subpopulations

African (AFR)

AF:

0.000186

AC:

AN:

32222

American (AMR)

AF:

0.0000477

AC:

AN:

41906

Ashkenazi Jewish (ASJ)

AF:

0.0000399

AC:

AN:

25088

East Asian (EAS)

AF:

0.00

AC:

AN:

37728

South Asian (SAS)

AF:

0.00

AC:

AN:

78840

European-Finnish (FIN)

AF:

0.0000785

AC:

AN:

50954

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

0.000680

AC:

741

AN:

1088984

Other (OTH)

AF:

0.000292

AC:

AN:

58266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

107

142

178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

128

160

<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:

0.000381

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41514

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000736

AC:

AN:

67974

Other (OTH)

AF:

0.000473

AC:

AN:

2112

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:

0.000469

Hom.:

Bravo

AF:

0.000374

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

DNAH8-related disorder

Benign:1

Jan 14, 2020

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 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Mar 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DNAH8: BP4, BP7

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

4.6

(source)

DANN

Benign

0.74

PhyloP100

0.014

Mutation Taster

=100/0

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over