Genetic Variant DNAH8:p.Ala291Gly (chr6-38737176-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001206927.2(DNAH8):c.872C>G(p.Ala291Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,420,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A291V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.47

Publications

0 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=0.1987963).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2 link	c.872C>G	p.Ala291Gly	missense_variant	Exon 6 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
DNAH8	ENST00000327475.11 link	c.872C>G	p.Ala291Gly	missense_variant	Exon 6 of 93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7 link	c.221C>G	p.Ala74Gly	missense_variant	Exon 4 of 91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6 link	c.872C>G	p.Ala291Gly	missense_variant	Exon 5 of 82	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.04e-7

AC:

AN:

1420746

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

705792

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31808

American (AMR)

AF:

0.00

AC:

AN:

37812

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25212

East Asian (EAS)

AF:

0.00

AC:

AN:

37534

South Asian (SAS)

AF:

0.00

AC:

AN:

78272

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52542

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5654

European-Non Finnish (NFE)

AF:

9.15e-7

AC:

AN:

1093196

Other (OTH)

AF:

0.00

AC:

AN:

58716

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;T;T

Eigen

Benign

-0.073

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;.;M

PhyloP100

2.5

PrimateAI

Benign

0.34

PROVEAN

Benign

0.0

.;N;N

REVEL

Benign

0.051

Sift

Pathogenic

0.0

.;T;T

Sift4G

Pathogenic

0.0

.;.;.

Vest4

0.27

ClinPred

0.79

GERP RS

5.2

Varity_R

0.11

gMVP

0.31

Mutation Taster

=86/14

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over