Variant rs4714192 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001206927.2(DNAH8):c.8154C>T(p.Tyr2718=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,580,476 control chromosomes in the GnomAD database, including 46,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3799 hom., cov: 32)

Exomes 𝑓: 0.24 ( 42812 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.322

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 6-38883893-C-T is Benign according to our data. Variant chr6-38883893-C-T is described in ClinVar as [Benign]. Clinvar id is 402768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.322 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.8154C>T	p.Tyr2718=	synonymous_variant	56/93	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.8154C>T	p.Tyr2718=	synonymous_variant	56/93	5	NM_001206927.2	ENSP00000333363	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.7503C>T	p.Tyr2501=	synonymous_variant	54/91	2		ENSP00000352312	A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.8154C>T	p.Tyr2718=	synonymous_variant	55/82	5		ENSP00000415331

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32537

AN:

151776

Hom.:

3793

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.218

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.364

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.239

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.212

GnomAD3 exomes

AF:

0.244

AC:

58462

AN:

239342

Hom.:

7577

AF XY:

0.247

AC XY:

32029

AN XY:

129880

show subpopulations

Gnomad AFR exome

AF:

0.144

Gnomad AMR exome

AF:

0.242

Gnomad ASJ exome

AF:

0.178

Gnomad EAS exome

AF:

0.366

Gnomad SAS exome

AF:

0.320

Gnomad FIN exome

AF:

0.197

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.207

GnomAD4 exome

AF:

0.241

AC:

344341

AN:

1428580

Hom.:

42812

Cov.:

AF XY:

0.243

AC XY:

172548

AN XY:

710252

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.238

Gnomad4 ASJ exome

AF:

0.174

Gnomad4 EAS exome

AF:

0.326

Gnomad4 SAS exome

AF:

0.321

Gnomad4 FIN exome

AF:

0.197

Gnomad4 NFE exome

AF:

0.239

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.214

AC:

32558

AN:

151896

Hom.:

3799

Cov.:

AF XY:

0.215

AC XY:

15949

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.152

Gnomad4 AMR

AF:

0.214

Gnomad4 ASJ

AF:

0.172

Gnomad4 EAS

AF:

0.365

Gnomad4 SAS

AF:

0.331

Gnomad4 FIN

AF:

0.203

Gnomad4 NFE

AF:

0.237

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.226

Hom.:

8066

Bravo

AF:

0.210

Asia WGS

AF:

0.305

AC:

1055

AN:

3454

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

0.50

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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