Variant rs77769111 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 3P and 16B. PVS1_ModeratePP3BP6_Very_StrongBA1

The NM_001206927.2(DNAH8):c.1764+2T>C variant causes a splice donor change. The variant allele was found at a frequency of 0.00394 in 1,595,600 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 123 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 75 hom. )

Consequence

DNAH8
NM_001206927.2 splice_donor

Scores

Splicing: ADA: 0.9947

Clinical Significance

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

Conservation

PhyloP100: 6.03

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 -13 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.010337015 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, max_spliceai. No scorers claiming Uncertain. Scorers claiming Benign: dbscSNV1_RF.

BP6

Variant 6-38770561-T-C is Benign according to our data. Variant chr6-38770561-T-C is described in ClinVar as [Benign]. Clinvar id is 414428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.1764+2T>C		splice_donor_variant		ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11 linkuse as main transcript	c.1764+2T>C	splice_donor_variant	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.1113+2T>C	splice_donor_variant	2		A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.1764+2T>C	splice_donor_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0213

AC:

3237

AN:

152156

Hom.:

121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0734

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00883

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:

0.000470

Gnomad OTH

AF:

0.0149

GnomAD3 exomes

AF:

0.00570

AC:

1317

AN:

231170

Hom.:

AF XY:

0.00411

AC XY:

513

AN XY:

124806

show subpopulations

Gnomad AFR exome

AF:

0.0695

Gnomad AMR exome

AF:

0.00506

Gnomad ASJ exome

AF:

0.000229

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000784

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000466

Gnomad OTH exome

AF:

0.00161

GnomAD4 exome

AF:

0.00211

AC:

3042

AN:

1443326

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

1340

AN XY:

717530

show subpopulations

Gnomad4 AFR exome

AF:

0.0708

Gnomad4 AMR exome

AF:

0.00522

Gnomad4 ASJ exome

AF:

0.0000399

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000732

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000201

Gnomad4 OTH exome

AF:

0.00472

GnomAD4 genome

AF:

0.0213

AC:

3250

AN:

152274

Hom.:

123

Cov.:

AF XY:

0.0207

AC XY:

1543

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0735

Gnomad4 AMR

AF:

0.00882

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00241

Hom.:

Bravo

AF:

0.0234

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0647

AC:

285

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00666

AC:

809

Asia WGS

AF:

0.00462

AC:

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

Invitae

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 06, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Pathogenic

0.99

MutationTaster

Benign

1.0

D;D;D

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Benign

0.67

SpliceAI score (max)

0.95

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.95

Position offset: -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