Variant rs139961713 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.2915A>T(p.Glu972Val) variant causes a missense change. The variant allele was found at a frequency of 0.0033 in 1,599,432 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 117 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.07

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=0.0049007535).

BP6

Variant 6-38803192-A-T is Benign according to our data. Variant chr6-38803192-A-T is described in ClinVar as [Benign]. Clinvar id is 224928.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00291 (443/152344) while in subpopulation SAS AF= 0.0377 (182/4832). AF 95% confidence interval is 0.0332. There are 6 homozygotes in gnomad4. There are 280 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.2915A>T	p.Glu972Val	missense_variant	22/93	ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11 linkuse as main transcript	c.2915A>T	p.Glu972Val	missense_variant	22/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.2264A>T	p.Glu755Val	missense_variant	20/91	2		A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.2915A>T	p.Glu972Val	missense_variant	21/82	5

Frequencies

GnomAD3 genomes

AF:

0.00292

AC:

445

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0360

Gnomad SAS

AF:

0.0376

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00732

AC:

1767

AN:

241424

Hom.:

AF XY:

0.00887

AC XY:

1156

AN XY:

130330

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.00105

Gnomad ASJ exome

AF:

0.000405

Gnomad EAS exome

AF:

0.0349

Gnomad SAS exome

AF:

0.0362

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000682

Gnomad OTH exome

AF:

0.00449

GnomAD4 exome

AF:

0.00334

AC:

4840

AN:

1447088

Hom.:

117

Cov.:

AF XY:

0.00427

AC XY:

3071

AN XY:

719250

show subpopulations

Gnomad4 AFR exome

AF:

0.000364

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.000155

Gnomad4 EAS exome

AF:

0.0294

Gnomad4 SAS exome

AF:

0.0340

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000460

Gnomad4 OTH exome

AF:

0.00435

GnomAD4 genome

AF:

0.00291

AC:

443

AN:

152344

Hom.:

Cov.:

AF XY:

0.00376

AC XY:

280

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0357

Gnomad4 SAS

AF:

0.0377

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00211

Hom.:

Bravo

AF:

0.00242

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00825

AC:

1002

Asia WGS

AF:

0.0320

AC:

110

AN:

3478

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

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.032

T;T;T

Eigen

Benign

0.061

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.75

T;T;T

MetaRNN

Benign

0.0049

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

.;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.6

.;D;D

REVEL

Benign

0.17

Sift

Benign

0.16

.;T;T

Polyphen

0.026

.;.;B

Vest4

0.74

MVP

0.60

MPC

0.16

ClinPred

0.022

GERP RS

5.6

Varity_R

0.28

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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