Variant chr6-38931867-T-A 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.11331T>A(p.Thr3777Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,610,798 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 24 hom., cov: 31)

Exomes 𝑓: 0.012 ( 182 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.318

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:

DNAH8 (HGNC:):

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=-0.76).

BP6

Variant 6-38931867-T-A is Benign according to our data. Variant chr6-38931867-T-A is described in ClinVar as [Benign]. Clinvar id is 414412.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.318 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0109 (1655/152214) while in subpopulation SAS AF= 0.0401 (193/4818). AF 95% confidence interval is 0.0354. There are 24 homozygotes in gnomad4. There are 882 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.11331T>A	p.Thr3777Thr	synonymous_variant	76/93	ENST00000327475.11	NP_001193856.1	Q96JB1Q8IU65A0A075B6F3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11 linkuse as main transcript	c.11331T>A	p.Thr3777Thr	synonymous_variant	76/93	5	NM_001206927.2	ENSP00000333363.7		A0A075B6F3

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1648

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00466

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0213

Gnomad ASJ

AF:

0.0259

Gnomad EAS

AF:

0.0260

Gnomad SAS

AF:

0.0394

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00935

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.0142

AC:

3531

AN:

248108

Hom.:

AF XY:

0.0154

AC XY:

2067

AN XY:

134144

show subpopulations

Gnomad AFR exome

AF:

0.00484

Gnomad AMR exome

AF:

0.0112

Gnomad ASJ exome

AF:

0.0250

Gnomad EAS exome

AF:

0.0257

Gnomad SAS exome

AF:

0.0338

Gnomad FIN exome

AF:

0.00167

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.0186

GnomAD4 exome

AF:

0.0121

AC:

17643

AN:

1458584

Hom.:

182

Cov.:

AF XY:

0.0127

AC XY:

9240

AN XY:

725650

show subpopulations

Gnomad4 AFR exome

AF:

0.00477

Gnomad4 AMR exome

AF:

0.0117

Gnomad4 ASJ exome

AF:

0.0246

Gnomad4 EAS exome

AF:

0.0289

Gnomad4 SAS exome

AF:

0.0327

Gnomad4 FIN exome

AF:

0.00199

Gnomad4 NFE exome

AF:

0.0101

Gnomad4 OTH exome

AF:

0.0163

GnomAD4 genome

AF:

0.0109

AC:

1655

AN:

152214

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

882

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00467

Gnomad4 AMR

AF:

0.0213

Gnomad4 ASJ

AF:

0.0259

Gnomad4 EAS

AF:

0.0259

Gnomad4 SAS

AF:

0.0401

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00935

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.0110

Asia WGS

AF:

0.0290

AC:

101

AN:

3478

EpiCase

AF:

0.0107

EpiControl

AF:

0.0130

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 28, 2024

- -

DNAH8-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.41

DANN

Benign

0.69

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