Variant rs862432 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001206927.2(DNAH8):c.7982C>A(p.Thr2661Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0142 in 1,596,264 control chromosomes in the GnomAD database, including 1,974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 999 hom., cov: 33)

Exomes 𝑓: 0.0089 ( 975 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.92

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001779288).

BP6

Variant 6-38883033-C-A is Benign according to our data. Variant chr6-38883033-C-A is described in ClinVar as [Benign]. Clinvar id is 414377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-38883033-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.7982C>A	p.Thr2661Asn	missense_variant	54/93	ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11 linkuse as main transcript	c.7982C>A	p.Thr2661Asn	missense_variant	54/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.7331C>A	p.Thr2444Asn	missense_variant	52/91	2		A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.7982C>A	p.Thr2661Asn	missense_variant	53/82	5

Frequencies

GnomAD3 genomes

AF:

0.0650

AC:

9876

AN:

152012

Hom.:

995

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0328

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00309

Gnomad OTH

AF:

0.0527

GnomAD3 exomes

AF:

0.0200

AC:

4732

AN:

236978

Hom.:

426

AF XY:

0.0154

AC XY:

1967

AN XY:

128138

show subpopulations

Gnomad AFR exome

AF:

0.225

Gnomad AMR exome

AF:

0.0163

Gnomad ASJ exome

AF:

0.0285

Gnomad EAS exome

AF:

0.0000571

Gnomad SAS exome

AF:

0.00228

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00273

Gnomad OTH exome

AF:

0.0118

GnomAD4 exome

AF:

0.00885

AC:

12787

AN:

1444134

Hom.:

975

Cov.:

AF XY:

0.00805

AC XY:

5780

AN XY:

717874

show subpopulations

Gnomad4 AFR exome

AF:

0.230

Gnomad4 AMR exome

AF:

0.0189

Gnomad4 ASJ exome

AF:

0.0279

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00242

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.00213

Gnomad4 OTH exome

AF:

0.0182

GnomAD4 genome

AF:

0.0651

AC:

9904

AN:

152130

Hom.:

999

Cov.:

AF XY:

0.0633

AC XY:

4708

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.0328

Gnomad4 ASJ

AF:

0.0288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00309

Gnomad4 OTH

AF:

0.0521

Alfa

AF:

0.0148

Hom.:

365

Bravo

AF:

0.0760

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.208

AC:

915

ESP6500EA

AF:

0.00338

AC:

ExAC

AF:

0.0233

AC:

2825

Asia WGS

AF:

0.0140

AC:

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.081

T;T;T

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

D;D;D

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

.;.;M

MutationTaster

Benign

2.8e-7

P;P;P

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-4.5

.;D;D

REVEL

Uncertain

0.32

Sift

Benign

0.13

.;T;T

Polyphen

1.0

.;.;D

Vest4

0.61

MPC

0.60

ClinPred

0.022

GERP RS

5.9

Varity_R

0.63

gMVP

0.83

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