Variant rs61748643 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001206927.2(DNAH8):c.5127C>T(p.Leu1709=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,612,638 control chromosomes in the GnomAD database, including 204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 18 hom., cov: 32)

Exomes 𝑓: 0.011 ( 186 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.102

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 6-38848729-C-T is Benign according to our data. Variant chr6-38848729-C-T is described in ClinVar as [Benign]. Clinvar id is 238651.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.102 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0102 (1554/151928) while in subpopulation SAS AF= 0.0252 (121/4798). AF 95% confidence interval is 0.0216. There are 18 homozygotes in gnomad4. There are 799 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.5127C>T	p.Leu1709=	synonymous_variant	37/93	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.5127C>T	p.Leu1709=	synonymous_variant	37/93	5	NM_001206927.2	ENSP00000333363	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.4476C>T	p.Leu1492=	synonymous_variant	35/91	2		ENSP00000352312	A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.5127C>T	p.Leu1709=	synonymous_variant	36/82	5		ENSP00000415331

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1546

AN:

151810

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00414

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0167

Gnomad ASJ

AF:

0.0554

Gnomad EAS

AF:

0.0253

Gnomad SAS

AF:

0.0250

Gnomad FIN

AF:

0.00105

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00887

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0136

AC:

3402

AN:

251016

Hom.:

AF XY:

0.0142

AC XY:

1931

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.00431

Gnomad AMR exome

AF:

0.0107

Gnomad ASJ exome

AF:

0.0503

Gnomad EAS exome

AF:

0.0243

Gnomad SAS exome

AF:

0.0252

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00962

Gnomad OTH exome

AF:

0.0187

GnomAD4 exome

AF:

0.0115

AC:

16728

AN:

1460710

Hom.:

186

Cov.:

AF XY:

0.0118

AC XY:

8609

AN XY:

726698

show subpopulations

Gnomad4 AFR exome

AF:

0.00383

Gnomad4 AMR exome

AF:

0.0122

Gnomad4 ASJ exome

AF:

0.0498

Gnomad4 EAS exome

AF:

0.0244

Gnomad4 SAS exome

AF:

0.0238

Gnomad4 FIN exome

AF:

0.00199

Gnomad4 NFE exome

AF:

0.00948

Gnomad4 OTH exome

AF:

0.0167

GnomAD4 genome

AF:

0.0102

AC:

1554

AN:

151928

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

799

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.00422

Gnomad4 AMR

AF:

0.0167

Gnomad4 ASJ

AF:

0.0554

Gnomad4 EAS

AF:

0.0252

Gnomad4 SAS

AF:

0.0252

Gnomad4 FIN

AF:

0.00105

Gnomad4 NFE

AF:

0.00887

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0118

Hom.:

Bravo

AF:

0.0103

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.0115

EpiControl

AF:

0.0114

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.15

DANN

Benign

0.59

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