Variant rs6935293 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.863A>G(p.Asn288Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 1,582,706 control chromosomes in the GnomAD database, including 1,721 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 176 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1545 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.66

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=0.0023658872).

BP6

Variant 6-38737167-A-G is Benign according to our data. Variant chr6-38737167-A-G is described in ClinVar as [Benign]. Clinvar id is 414419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.089 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.863A>G	p.Asn288Ser	missense_variant	6/93	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.863A>G	p.Asn288Ser	missense_variant	6/93	5	NM_001206927.2	ENSP00000333363	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.212A>G	p.Asn71Ser	missense_variant	4/91	2		ENSP00000352312	A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.863A>G	p.Asn288Ser	missense_variant	5/82	5		ENSP00000415331

Frequencies

GnomAD3 genomes

AF:

0.0453

AC:

6897

AN:

152180

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0378

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0416

Gnomad ASJ

AF:

0.0464

Gnomad EAS

AF:

0.0956

Gnomad SAS

AF:

0.0474

Gnomad FIN

AF:

0.0759

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0413

Gnomad OTH

AF:

0.0521

GnomAD3 exomes

AF:

0.0425

AC:

9749

AN:

229310

Hom.:

217

AF XY:

0.0421

AC XY:

5252

AN XY:

124840

show subpopulations

Gnomad AFR exome

AF:

0.0326

Gnomad AMR exome

AF:

0.0317

Gnomad ASJ exome

AF:

0.0391

Gnomad EAS exome

AF:

0.0641

Gnomad SAS exome

AF:

0.0382

Gnomad FIN exome

AF:

0.0739

Gnomad NFE exome

AF:

0.0386

Gnomad OTH exome

AF:

0.0437

GnomAD4 exome

AF:

0.0417

AC:

59659

AN:

1430408

Hom.:

1545

Cov.:

AF XY:

0.0417

AC XY:

29628

AN XY:

711010

show subpopulations

Gnomad4 AFR exome

AF:

0.0369

Gnomad4 AMR exome

AF:

0.0344

Gnomad4 ASJ exome

AF:

0.0419

Gnomad4 EAS exome

AF:

0.117

Gnomad4 SAS exome

AF:

0.0402

Gnomad4 FIN exome

AF:

0.0724

Gnomad4 NFE exome

AF:

0.0379

Gnomad4 OTH exome

AF:

0.0430

GnomAD4 genome

AF:

0.0453

AC:

6898

AN:

152298

Hom.:

176

Cov.:

AF XY:

0.0468

AC XY:

3488

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0378

Gnomad4 AMR

AF:

0.0415

Gnomad4 ASJ

AF:

0.0464

Gnomad4 EAS

AF:

0.0960

Gnomad4 SAS

AF:

0.0472

Gnomad4 FIN

AF:

0.0759

Gnomad4 NFE

AF:

0.0413

Gnomad4 OTH

AF:

0.0543

Alfa

AF:

0.0431

Hom.:

163

Bravo

AF:

0.0425

TwinsUK

AF:

0.0375

AC:

139

ALSPAC

AF:

0.0345

AC:

133

ESP6500AA

AF:

0.0343

AC:

151

ESP6500EA

AF:

0.0407

AC:

350

ExAC

AF:

0.0486

AC:

5907

Asia WGS

AF:

0.0790

AC:

273

AN:

3478

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 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

0.075

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.020

T;T;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.55

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.74

T;T;T

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;.;L

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.4

.;N;N

REVEL

Benign

0.12

Sift

Benign

0.53

.;T;T

Polyphen

0.011

.;.;B

Vest4

0.056

MPC

0.11

ClinPred

0.0037

GERP RS

2.8

Varity_R

0.070

gMVP

0.47

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