dbSNP rs754105184: DNAH8:p.Ala16Gly (chr6-38722856-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.47C>G(p.Ala16Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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. A16V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.577

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=0.11763483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2 link	c.47C>G	p.Ala16Gly	missense_variant	Exon 2 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.47C>G	p.Ala16Gly	missense_variant	Exon 2 of 93	5	NM_001206927.2	ENSP00000333363.7	A0A075B6F3
DNAH8	ENST00000373278.8 link	c.47C>G	p.Ala16Gly	missense_variant	Exon 2 of 5	1		ENSP00000362375.4	Q8IU65
DNAH8	ENST00000449981.6 link	c.47C>G	p.Ala16Gly	missense_variant	Exon 1 of 82	5		ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458280

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725250

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33374

American (AMR)

AF:

0.00

AC:

AN:

44430

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26036

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

85952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52154

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1110738

Other (OTH)

AF:

0.00

AC:

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0079

T;.;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.46

T;T;T

M_CAP

Benign

0.0079

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.1

PhyloP100

0.58

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.88

.;N;N

REVEL

Benign

0.063

Sift

Benign

0.064

.;T;T

Sift4G

Pathogenic

0.0

.;D;.

Polyphen

0.97

.;D;.

Vest4

0.20

MutPred

0.27

Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);

MVP

0.27

ClinPred

0.89

GERP RS

3.1

PromoterAI

-0.54

Under-expression

(source)

gMVP

0.12

Mutation Taster

=98/2

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.

rs754105184

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over