Variant rs58784538 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001206927.2(DNAH8):c.1617+3T>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0037 in 1,503,474 control chromosomes in the GnomAD database, including 196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 111 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 85 hom. )

Consequence

DNAH8
NM_001206927.2 splice_donor_region, intron

Scores

Splicing: ADA: 0.001981

Clinical Significance

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

Conservation

PhyloP100: 1.91

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 6-38761806-T-G is Benign according to our data. Variant chr6-38761806-T-G is described in ClinVar as [Benign]. Clinvar id is 414413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0673 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.1617+3T>G		splice_donor_region_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.1617+3T>G	splice_donor_region_variant, intron_variant	5	NM_001206927.2	ENSP00000333363	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.966+3T>G	splice_donor_region_variant, intron_variant	2		ENSP00000352312	A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.1617+3T>G	splice_donor_region_variant, intron_variant	5		ENSP00000415331

Frequencies

GnomAD3 genomes

AF:

0.0199

AC:

3027

AN:

152194

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0696

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00629

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00548

AC:

1043

AN:

190208

Hom.:

AF XY:

0.00381

AC XY:

399

AN XY:

104810

show subpopulations

Gnomad AFR exome

AF:

0.0724

Gnomad AMR exome

AF:

0.00453

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000897

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000195

Gnomad OTH exome

AF:

0.00242

GnomAD4 exome

AF:

0.00188

AC:

2534

AN:

1351162

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

1115

AN XY:

675310

show subpopulations

Gnomad4 AFR exome

AF:

0.0720

Gnomad4 AMR exome

AF:

0.00459

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000155

Gnomad4 OTH exome

AF:

0.00397

GnomAD4 genome

AF:

0.0199

AC:

3028

AN:

152312

Hom.:

111

Cov.:

AF XY:

0.0186

AC XY:

1383

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0695

Gnomad4 AMR

AF:

0.00628

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00995

Hom.:

Bravo

AF:

0.0229

Asia WGS

AF:

0.00289

AC:

AN:

3476

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 25, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0020

dbscSNV1_RF

Benign

0.052

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