Variant rs141263020 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.10678G>A(p.Ala3560Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,613,156 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 6 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.87

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-AS1 (HGNC:):

DNAH8-AS1 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=0.03558153).

BP6

Variant 6-38923073-G-A is Benign according to our data. Variant chr6-38923073-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 238629.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00206 (313/152216) while in subpopulation NFE AF= 0.00241 (164/68008). AF 95% confidence interval is 0.00211. There are 1 homozygotes in gnomad4. There are 156 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.10678G>A	p.Ala3560Thr	missense_variant	72/93	ENST00000327475.11	NP_001193856.1	Q96JB1Q8IU65A0A075B6F3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11 linkuse as main transcript	c.10678G>A	p.Ala3560Thr	missense_variant	72/93	5	NM_001206927.2	ENSP00000333363.7		A0A075B6F3

Frequencies

GnomAD3 genomes

AF:

0.00206

AC:

313

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.0648

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00594

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00241

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00219

AC:

549

AN:

250322

Hom.:

AF XY:

0.00214

AC XY:

289

AN XY:

135284

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00588

Gnomad NFE exome

AF:

0.00350

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.00211

AC:

3089

AN:

1460940

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

1531

AN XY:

726746

show subpopulations

Gnomad4 AFR exome

AF:

0.000419

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00630

Gnomad4 NFE exome

AF:

0.00235

Gnomad4 OTH exome

AF:

0.00179

GnomAD4 genome

AF:

0.00206

AC:

313

AN:

152216

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

156

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00594

Gnomad4 NFE

AF:

0.00241

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00178

Hom.:

Bravo

AF:

0.00163

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00270

AC:

328

EpiCase

AF:

0.00175

EpiControl

AF:

0.00231

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 06, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Uncertain

0.13

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

T;D;T

Eigen

Pathogenic

0.96

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.036

T;T;T

MetaSVM

Uncertain

0.63

MutationAssessor

Pathogenic

4.0

.;.;H

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.7

.;D;D

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0010

.;D;D

Polyphen

1.0

.;.;D

Vest4

0.78

MVP

0.79

MPC

0.56

ClinPred

0.14

GERP RS

5.5

Varity_R

0.62

gMVP

0.50

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