Variant rs45529837 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001206927.2(DNAH8):c.2620G>A(p.Val874Met) variant causes a missense change. The variant allele was found at a frequency of 0.0289 in 1,612,376 control chromosomes in the GnomAD database, including 791 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 67 hom., cov: 33)

Exomes 𝑓: 0.029 ( 724 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.58

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003100425).

BP6

Variant 6-38789839-G-A is Benign according to our data. Variant chr6-38789839-G-A is described in ClinVar as [Benign]. Clinvar id is 414389.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-38789839-G-A is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.2620G>A	p.Val874Met	missense_variant	19/93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11 linkuse as main transcript	c.2620G>A	p.Val874Met	missense_variant	19/93	5	NM_001206927.2	ENSP00000333363	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.1969G>A	p.Val657Met	missense_variant	17/91	2		ENSP00000352312	A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.2620G>A	p.Val874Met	missense_variant	18/82	5		ENSP00000415331

Frequencies

GnomAD3 genomes

AF:

0.0261

AC:

3967

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0143

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0437

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.000961

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.0219

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0307

Gnomad OTH

AF:

0.0516

GnomAD3 exomes

AF:

0.0249

AC:

6238

AN:

250822

Hom.:

112

AF XY:

0.0256

AC XY:

3475

AN XY:

135624

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.0282

Gnomad ASJ exome

AF:

0.0310

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0166

Gnomad FIN exome

AF:

0.0222

Gnomad NFE exome

AF:

0.0311

Gnomad OTH exome

AF:

0.0351

GnomAD4 exome

AF:

0.0292

AC:

42676

AN:

1460104

Hom.:

724

Cov.:

AF XY:

0.0290

AC XY:

21089

AN XY:

726444

show subpopulations

Gnomad4 AFR exome

AF:

0.0127

Gnomad4 AMR exome

AF:

0.0308

Gnomad4 ASJ exome

AF:

0.0324

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.0166

Gnomad4 FIN exome

AF:

0.0215

Gnomad4 NFE exome

AF:

0.0318

Gnomad4 OTH exome

AF:

0.0293

GnomAD4 genome

AF:

0.0260

AC:

3958

AN:

152272

Hom.:

Cov.:

AF XY:

0.0259

AC XY:

1926

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0142

Gnomad4 AMR

AF:

0.0436

Gnomad4 ASJ

AF:

0.0337

Gnomad4 EAS

AF:

0.000963

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.0219

Gnomad4 NFE

AF:

0.0307

Gnomad4 OTH

AF:

0.0510

Alfa

AF:

0.0302

Hom.:

115

Bravo

AF:

0.0284

TwinsUK

AF:

0.0302

AC:

112

ALSPAC

AF:

0.0257

AC:

ESP6500AA

AF:

0.0168

AC:

ESP6500EA

AF:

0.0343

AC:

295

ExAC

AF:

0.0250

AC:

3034

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.0327

EpiControl

AF:

0.0362

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

T;T;T

Eigen

Benign

0.10

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.84

T;T;T

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;.;L

MutationTaster

Benign

0.86

D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.96

.;N;N

REVEL

Benign

0.085

Sift

Benign

0.19

.;T;T

Polyphen

0.12

.;.;B

Vest4

0.23

MPC

0.47

ClinPred

0.011

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over