Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001206927.2(DNAH8):c.6G>C(p.Glu2Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,432,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E2E) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.295

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: 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07634148).

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.6G>C	p.Glu2Asp	missense	Exon 2 of 93	NP_001193856.1
	DNAH8	NM_001371.4		c.-561G>C		5_prime_UTR	Exon 2 of 92	NP_001362.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.6G>C	p.Glu2Asp	missense	Exon 2 of 93	ENSP00000333363.7
DNAH8	ENST00000373278.8	TSL:1	c.6G>C	p.Glu2Asp	missense	Exon 2 of 5	ENSP00000362375.4
DNAH8	ENST00000449981.6	TSL:5	c.6G>C	p.Glu2Asp	missense	Exon 1 of 82	ENSP00000415331.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000279

AC:

AN:

1432112

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

710196

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31994

American (AMR)

AF:

0.00

AC:

AN:

38374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24544

East Asian (EAS)

AF:

0.00

AC:

AN:

39364

South Asian (SAS)

AF:

0.00

AC:

AN:

82684

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5588

European-Non Finnish (NFE)

AF:

0.00000364

AC:

AN:

1098998

Other (OTH)

AF:

0.00

AC:

AN:

58934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.70

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0065

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.40

M_CAP

Benign

0.0054

MetaRNN

Benign

0.076

MetaSVM

Benign

-0.96

PhyloP100

-0.29

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.72

REVEL

Benign

0.0080

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.098

MutPred

0.10

Loss of methylation at K3 (P = 0.0632)

MVP

0.061

ClinPred

0.087

GERP RS

-1.4

PromoterAI

0.061

Neutral

(source)

gMVP

0.088

Mutation Taster

=99/1

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.

6-38722815-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over