Variant rs45519938 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.5490C>A(p.Asp1830Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,613,428 control chromosomes in the GnomAD database, including 182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 17 hom., cov: 32)

Exomes 𝑓: 0.013 ( 165 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.05

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=0.011568546).

BP6

Variant 6-38852717-C-A is Benign according to our data. Variant chr6-38852717-C-A is described in ClinVar as [Benign]. Clinvar id is 238652.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-38852717-C-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0102 (1548/152292) while in subpopulation NFE AF= 0.0155 (1053/68032). AF 95% confidence interval is 0.0147. There are 17 homozygotes in gnomad4. There are 772 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.5490C>A	p.Asp1830Glu	missense_variant	40/93	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.5490C>A	p.Asp1830Glu	missense_variant	40/93	5	NM_001206927.2	ENSP00000333363	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.4839C>A	p.Asp1613Glu	missense_variant	38/91	2		ENSP00000352312	A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.5490C>A	p.Asp1830Glu	missense_variant	39/82	5		ENSP00000415331

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1548

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00910

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0200

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0155

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.0101

AC:

2545

AN:

251038

Hom.:

AF XY:

0.0103

AC XY:

1393

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.00814

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00245

Gnomad FIN exome

AF:

0.0181

Gnomad NFE exome

AF:

0.0155

Gnomad OTH exome

AF:

0.0129

GnomAD4 exome

AF:

0.0129

AC:

18819

AN:

1461136

Hom.:

165

Cov.:

AF XY:

0.0127

AC XY:

9213

AN XY:

726902

show subpopulations

Gnomad4 AFR exome

AF:

0.00206

Gnomad4 AMR exome

AF:

0.00360

Gnomad4 ASJ exome

AF:

0.00926

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00215

Gnomad4 FIN exome

AF:

0.0184

Gnomad4 NFE exome

AF:

0.0148

Gnomad4 OTH exome

AF:

0.0113

GnomAD4 genome

AF:

0.0102

AC:

1548

AN:

152292

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

772

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00233

Gnomad4 AMR

AF:

0.00908

Gnomad4 ASJ

AF:

0.00750

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0200

Gnomad4 NFE

AF:

0.0155

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.0138

Hom.:

Bravo

AF:

0.00867

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0158

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.0121

AC:

104

ExAC

AF:

0.0108

AC:

1314

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0139

EpiControl

AF:

0.0126

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 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.71

T;T;T

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.5

.;.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.2

.;D;D

REVEL

Benign

0.28

Sift

Benign

0.034

.;D;D

Polyphen

0.94

.;.;P

Vest4

0.40

MutPred

0.79

.;.;Gain of disorder (P = 0.1493);

MPC

0.43

ClinPred

0.011

GERP RS

4.0

Varity_R

0.40

gMVP

0.40

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