Variant rs200015017 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001206927.2(DNAH8):c.5364-5T>G variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.000891 in 1,577,762 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00077 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 12 hom. )

Consequence

DNAH8
NM_001206927.2 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.2163

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.80

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 6-38851567-T-G is Benign according to our data. Variant chr6-38851567-T-G is described in ClinVar as [Benign]. Clinvar id is 525562.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000775 (118/152330) while in subpopulation SAS AF= 0.0087 (42/4828). AF 95% confidence interval is 0.00661. There are 0 homozygotes in gnomad4. There are 69 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.5364-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11 linkuse as main transcript	c.5364-5T>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5	NM_001206927.2	ENSP00000333363	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.4713-5T>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000352312	A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.5364-5T>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000415331

Frequencies

GnomAD3 genomes

AF:

0.000775

AC:

118

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00869

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00130

AC:

302

AN:

233062

Hom.:

AF XY:

0.00160

AC XY:

201

AN XY:

125858

show subpopulations

Gnomad AFR exome

AF:

0.0000629

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00312

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00774

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.000532

Gnomad OTH exome

AF:

0.000525

GnomAD4 exome

AF:

0.000904

AC:

1288

AN:

1425432

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

820

AN XY:

709658

show subpopulations

Gnomad4 AFR exome

AF:

0.0000630

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00304

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00881

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000351

Gnomad4 OTH exome

AF:

0.00130

GnomAD4 genome

AF:

0.000775

AC:

118

AN:

152330

Hom.:

Cov.:

AF XY:

0.000926

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00870

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000779

Hom.:

Bravo

AF:

0.000669

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000873

EpiControl

AF:

0.000593

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 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.22

dbscSNV1_RF

Benign

0.37

SpliceAI score (max)

0.050

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