6-38832433-T-C

Variant names:

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.4300T>C(p.Leu1434Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,558,752 control chromosomes in the GnomAD database, including 22,506 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4275 hom., cov: 32)

Exomes 𝑓: 0.15 ( 18231 hom. )

Consequence

DNAH8
NM_001206927.2 splice_region, synonymous

Scores

Splicing: ADA: 0.00001586

Clinical Significance

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

Conservation

PhyloP100: -0.0940

Publications

15 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=-0.81).

BP6

Variant 6-38832433-T-C is Benign according to our data. Variant chr6-38832433-T-C is described in ClinVar as [Benign]. Clinvar id is 402764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.094 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2 link	c.4300T>C	p.Leu1434Leu	splice_region_variant, synonymous_variant	Exon 31 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.4300T>C	p.Leu1434Leu	splice_region_variant, synonymous_variant	Exon 31 of 93	5	NM_001206927.2	ENSP00000333363.7	A0A075B6F3
DNAH8	ENST00000359357.7 link	c.3649T>C	p.Leu1217Leu	splice_region_variant, synonymous_variant	Exon 29 of 91	2		ENSP00000352312.3	Q96JB1-1
DNAH8	ENST00000449981.6 link	c.4300T>C	p.Leu1434Leu	splice_region_variant, synonymous_variant	Exon 30 of 82	5		ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32149

AN:

151992

Hom.:

4259

Cov.:

show subpopulations

Gnomad AFR

AF:

0.366

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.0975

Gnomad EAS

AF:

0.286

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.199

GnomAD2 exomes

AF:

0.180

AC:

45028

AN:

249740

AF XY:

0.174

show subpopulations

Gnomad AFR exome

AF:

0.380

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.104

Gnomad EAS exome

AF:

0.299

Gnomad FIN exome

AF:

0.143

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.151

AC:

212869

AN:

1406642

Hom.:

18231

Cov.:

AF XY:

0.151

AC XY:

106525

AN XY:

703262

show subpopulations

African (AFR)

AF:

0.372

AC:

11886

AN:

31962

American (AMR)

AF:

0.198

AC:

8787

AN:

44452

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

2765

AN:

25784

East Asian (EAS)

AF:

0.318

AC:

12483

AN:

39248

South Asian (SAS)

AF:

0.200

AC:

16975

AN:

84928

European-Finnish (FIN)

AF:

0.142

AC:

7589

AN:

53362

Middle Eastern (MID)

AF:

0.131

AC:

738

AN:

5650

European-Non Finnish (NFE)

AF:

0.134

AC:

142455

AN:

1062788

Other (OTH)

AF:

0.157

AC:

9191

AN:

58468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

8256

16512

24769

33025

41281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.212

AC:

32194

AN:

152110

Hom.:

4275

Cov.:

AF XY:

0.210

AC XY:

15645

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.366

AC:

15177

AN:

41458

American (AMR)

AF:

0.182

AC:

2780

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0975

AC:

338

AN:

3466

East Asian (EAS)

AF:

0.286

AC:

1478

AN:

5172

South Asian (SAS)

AF:

0.199

AC:

957

AN:

4812

European-Finnish (FIN)

AF:

0.144

AC:

1522

AN:

10590

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9260

AN:

68004

Other (OTH)

AF:

0.197

AC:

417

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1240

2480

3719

4959

6199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.165

Hom.:

6429

Bravo

AF:

0.225

Asia WGS

AF:

0.234

AC:

814

AN:

3478

EpiCase

AF:

0.131

EpiControl

AF:

0.136

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

-0.81

CADD

Benign

0.32

(source)

DANN

Benign

0.65

PhyloP100

-0.094

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.0

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.

6-38832433-T-C

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