Variant rs1678744 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001206927.2(DNAH8):c.5196T>C(p.Pro1732=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 1,612,938 control chromosomes in the GnomAD database, including 5,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 2560 hom., cov: 32)

Exomes 𝑓: 0.013 ( 2512 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.631

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 6-38848798-T-C is Benign according to our data. Variant chr6-38848798-T-C is described in ClinVar as [Benign]. Clinvar id is 414401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-38848798-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.631 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 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.5196T>C	p.Pro1732=	synonymous_variant	37/93	ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11 linkuse as main transcript	c.5196T>C	p.Pro1732=	synonymous_variant	37/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.4545T>C	p.Pro1515=	synonymous_variant	35/91	2		A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.5196T>C	p.Pro1732=	synonymous_variant	36/82	5

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15656

AN:

151990

Hom.:

2550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0512

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.00393

Gnomad OTH

AF:

0.0908

GnomAD3 exomes

AF:

0.0305

AC:

7645

AN:

250764

Hom.:

1105

AF XY:

0.0233

AC XY:

3152

AN XY:

135544

show subpopulations

Gnomad AFR exome

AF:

0.364

Gnomad AMR exome

AF:

0.0245

Gnomad ASJ exome

AF:

0.0277

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00282

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00359

Gnomad OTH exome

AF:

0.0191

GnomAD4 exome

AF:

0.0135

AC:

19711

AN:

1460830

Hom.:

2512

Cov.:

AF XY:

0.0122

AC XY:

8831

AN XY:

726722

show subpopulations

Gnomad4 AFR exome

AF:

0.368

Gnomad4 AMR exome

AF:

0.0284

Gnomad4 ASJ exome

AF:

0.0281

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00312

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00283

Gnomad4 OTH exome

AF:

0.0285

GnomAD4 genome

AF:

0.103

AC:

15698

AN:

152108

Hom.:

2560

Cov.:

AF XY:

0.0998

AC XY:

7426

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.346

Gnomad4 AMR

AF:

0.0511

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00393

Gnomad4 OTH

AF:

0.0898

Alfa

AF:

0.0307

Hom.:

796

Bravo

AF:

0.122

Asia WGS

AF:

0.0240

AC:

AN:

3478

EpiCase

AF:

0.00404

EpiControl

AF:

0.00462

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.8

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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