Variant rs116401640 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001206927.2(DNAH8):c.8338A>G(p.Ile2780Val) variant causes a missense change. The variant allele was found at a frequency of 0.000687 in 1,614,066 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 3 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.31

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:

DNAH8 (HGNC:):

DNAH8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008222312).

BP6

Variant 6-38886869-A-G is Benign according to our data. Variant chr6-38886869-A-G is described in ClinVar as [Benign]. Clinvar id is 414383.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00391 (596/152306) while in subpopulation AFR AF= 0.014 (582/41564). AF 95% confidence interval is 0.0131. There are 5 homozygotes in gnomad4. There are 294 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.8338A>G	p.Ile2780Val	missense_variant	57/93	ENST00000327475.11	NP_001193856.1	Q96JB1Q8IU65A0A075B6F3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAH8	ENST00000327475.11 linkuse as main transcript	c.8338A>G	p.Ile2780Val	missense_variant	57/93	5	NM_001206927.2	ENSP00000333363.7	A0A075B6F3
DNAH8	ENST00000359357.7 linkuse as main transcript	c.7687A>G	p.Ile2563Val	missense_variant	55/91	2		ENSP00000352312.3	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.8338A>G	p.Ile2780Val	missense_variant	56/82	5		ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes

AF:

0.00388

AC:

591

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000912

AC:

229

AN:

251152

Hom.:

AF XY:

0.000678

AC XY:

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.0123

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000351

AC:

513

AN:

1461760

Hom.:

Cov.:

AF XY:

0.000311

AC XY:

226

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.0124

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.00391

AC:

596

AN:

152306

Hom.:

Cov.:

AF XY:

0.00395

AC XY:

294

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0140

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000611

Hom.:

Bravo

AF:

0.00404

ESP6500AA

AF:

0.0148

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00114

AC:

139

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 25, 2024

- -

DNAH8-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 05, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

T;T;T

Eigen

Benign

-0.060

Eigen_PC

Benign

0.053

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

T;T;T

MetaRNN

Benign

0.0082

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

.;.;L

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.84

.;N;N

REVEL

Benign

0.064

Sift

Benign

0.091

.;T;T

Polyphen

0.48

.;.;P

Vest4

0.42

MVP

0.40

MPC

0.11

ClinPred

0.033

GERP RS

4.6

Varity_R

0.11

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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