Genetic Variant DNAH8:c.2584-201C>T (chr6-38789602-C-T) – 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.2584-201C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,926 control chromosomes in the GnomAD database, including 8,857 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.33 ( 8857 hom., cov: 32)

Consequence

DNAH8
NM_001206927.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.182

Publications

3 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=-0.88).

BP6

Variant 6-38789602-C-T is Benign according to our data. Variant chr6-38789602-C-T is described in ClinVar as Benign. ClinVar VariationId is 1236141.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.391 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.2584-201C>T		intron	N/A	NP_001193856.1	A0A075B6F3
	DNAH8	NM_001371.4		c.1933-201C>T		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.2584-201C>T	intron	N/A	ENSP00000333363.7	A0A075B6F3
DNAH8	ENST00000359357.7	TSL:2	c.1933-201C>T	intron	N/A	ENSP00000352312.3	Q96JB1-1
DNAH8	ENST00000449981.6	TSL:5	c.2584-201C>T	intron	N/A	ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

50738

AN:

151808

Hom.:

8858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.379

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.390

Gnomad SAS

AF:

0.404

Gnomad FIN

AF:

0.326

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.352

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

GnomAD4 genome

AF:

0.334

AC:

50752

AN:

151926

Hom.:

8857

Cov.:

AF XY:

0.334

AC XY:

24828

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.260

AC:

10764

AN:

41432

American (AMR)

AF:

0.313

AC:

4773

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

1518

AN:

3468

East Asian (EAS)

AF:

0.391

AC:

2015

AN:

5158

South Asian (SAS)

AF:

0.405

AC:

1952

AN:

4814

European-Finnish (FIN)

AF:

0.326

AC:

3441

AN:

10548

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.369

AC:

25091

AN:

67920

Other (OTH)

AF:

0.351

AC:

741

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1735

3469

5204

6938

8673

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<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:

0.361

Hom.:

28174

Bravo

AF:

0.331

Asia WGS

AF:

0.359

AC:

1251

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

-0.88

CADD

Benign

1.4

(source)

DANN

Benign

0.37

PhyloP100

-0.18

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