Genetic Variant DNAH8:c.6310+176A>G (chr6-38862634-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001206927.2(DNAH8):c.6310+176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,016 control chromosomes in the GnomAD database, including 14,154 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)

Consequence

DNAH8
NM_001206927.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.74

Publications

4 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-38862634-A-G is Benign according to our data. Variant chr6-38862634-A-G is described in ClinVar as Benign. ClinVar VariationId is 1256848.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 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.6310+176A>G		intron	N/A	NP_001193856.1	A0A075B6F3
	DNAH8	NM_001371.4		c.5659+176A>G		intron	N/A	NP_001362.2	Q96JB1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.6310+176A>G	intron	N/A	ENSP00000333363.7	A0A075B6F3
DNAH8	ENST00000359357.7	TSL:2	c.5659+176A>G	intron	N/A	ENSP00000352312.3	Q96JB1-1
DNAH8	ENST00000449981.6	TSL:5	c.6310+176A>G	intron	N/A	ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes

AF:

0.421

AC:

64017

AN:

151898

Hom.:

14113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.366

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.693

Gnomad SAS

AF:

0.459

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.413

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.422

AC:

64113

AN:

152016

Hom.:

14154

Cov.:

AF XY:

0.421

AC XY:

31279

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.367

AC:

15212

AN:

41462

American (AMR)

AF:

0.523

AC:

7983

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

1230

AN:

3468

East Asian (EAS)

AF:

0.694

AC:

3580

AN:

5160

South Asian (SAS)

AF:

0.458

AC:

2202

AN:

4806

European-Finnish (FIN)

AF:

0.370

AC:

3905

AN:

10560

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.421

AC:

28590

AN:

67964

Other (OTH)

AF:

0.419

AC:

886

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1834

3668

5502

7336

9170

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:

0.431

Hom.:

47842

Bravo

AF:

0.431

Asia WGS

AF:

0.574

AC:

1997

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.035

(source)

DANN

Benign

0.26

PhyloP100

-1.7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over