Variant 6-38857553-C-T 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.5769C>T(p.His1923=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,610,598 control chromosomes in the GnomAD database, including 156,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14154 hom., cov: 32)

Exomes 𝑓: 0.44 ( 142448 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.00900

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=-0.38).

BP6

Variant 6-38857553-C-T is Benign according to our data. Variant chr6-38857553-C-T is described in ClinVar as [Benign]. Clinvar id is 402765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.009 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 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.5769C>T	p.His1923=	synonymous_variant	42/93	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.5769C>T	p.His1923=	synonymous_variant	42/93	5	NM_001206927.2	ENSP00000333363	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.5118C>T	p.His1706=	synonymous_variant	40/91	2		ENSP00000352312	A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.5769C>T	p.His1923=	synonymous_variant	41/82	5		ENSP00000415331

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

63975

AN:

151716

Hom.:

14113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.366

Gnomad AMI

AF:

0.443

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.693

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.413

GnomAD3 exomes

AF:

0.462

AC:

115703

AN:

250498

Hom.:

28279

AF XY:

0.452

AC XY:

61200

AN XY:

135380

show subpopulations

Gnomad AFR exome

AF:

0.365

Gnomad AMR exome

AF:

0.625

Gnomad ASJ exome

AF:

0.360

Gnomad EAS exome

AF:

0.707

Gnomad SAS exome

AF:

0.446

Gnomad FIN exome

AF:

0.372

Gnomad NFE exome

AF:

0.419

Gnomad OTH exome

AF:

0.416

GnomAD4 exome

AF:

0.437

AC:

637100

AN:

1458764

Hom.:

142448

Cov.:

AF XY:

0.435

AC XY:

315486

AN XY:

725748

show subpopulations

Gnomad4 AFR exome

AF:

0.355

Gnomad4 AMR exome

AF:

0.613

Gnomad4 ASJ exome

AF:

0.359

Gnomad4 EAS exome

AF:

0.689

Gnomad4 SAS exome

AF:

0.441

Gnomad4 FIN exome

AF:

0.374

Gnomad4 NFE exome

AF:

0.428

Gnomad4 OTH exome

AF:

0.439

GnomAD4 genome

AF:

0.422

AC:

64070

AN:

151834

Hom.:

14154

Cov.:

AF XY:

0.421

AC XY:

31251

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.367

Gnomad4 AMR

AF:

0.523

Gnomad4 ASJ

AF:

0.355

Gnomad4 EAS

AF:

0.693

Gnomad4 SAS

AF:

0.457

Gnomad4 FIN

AF:

0.371

Gnomad4 NFE

AF:

0.421

Gnomad4 OTH

AF:

0.418

Alfa

AF:

0.410

Hom.:

14938

Bravo

AF:

0.431

Asia WGS

AF:

0.573

AC:

1992

AN:

3476

EpiCase

AF:

0.418

EpiControl

AF:

0.406

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

-0.38

CADD

Benign

2.5

DANN

Benign

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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