Variant rs3737094 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.13119A>G(p.Leu4373=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,592,200 control chromosomes in the GnomAD database, including 149,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12565 hom., cov: 32)

Exomes 𝑓: 0.43 ( 136515 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.316

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=-0.91).

BP6

Variant 6-38990077-A-G is Benign according to our data. Variant chr6-38990077-A-G is described in ClinVar as [Benign]. Clinvar id is 257629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-38990077-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.316 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 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.13119A>G	p.Leu4373=	synonymous_variant	88/93	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.13119A>G	p.Leu4373=	synonymous_variant	88/93	5	NM_001206927.2	ENSP00000333363	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.12468A>G	p.Leu4156=	synonymous_variant	86/91	2		ENSP00000352312	A2	Q96JB1-1

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60734

AN:

151854

Hom.:

12554

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.390

Gnomad EAS

AF:

0.254

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.446

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.399

GnomAD3 exomes

AF:

0.392

AC:

98333

AN:

250694

Hom.:

20301

AF XY:

0.393

AC XY:

53225

AN XY:

135514

show subpopulations

Gnomad AFR exome

AF:

0.326

Gnomad AMR exome

AF:

0.334

Gnomad ASJ exome

AF:

0.400

Gnomad EAS exome

AF:

0.255

Gnomad SAS exome

AF:

0.305

Gnomad FIN exome

AF:

0.439

Gnomad NFE exome

AF:

0.454

Gnomad OTH exome

AF:

0.424

GnomAD4 exome

AF:

0.430

AC:

619660

AN:

1440228

Hom.:

136515

Cov.:

AF XY:

0.428

AC XY:

307097

AN XY:

717998

show subpopulations

Gnomad4 AFR exome

AF:

0.324

Gnomad4 AMR exome

AF:

0.343

Gnomad4 ASJ exome

AF:

0.397

Gnomad4 EAS exome

AF:

0.240

Gnomad4 SAS exome

AF:

0.302

Gnomad4 FIN exome

AF:

0.446

Gnomad4 NFE exome

AF:

0.454

Gnomad4 OTH exome

AF:

0.424

GnomAD4 genome

AF:

0.400

AC:

60779

AN:

151972

Hom.:

12565

Cov.:

AF XY:

0.397

AC XY:

29470

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.336

Gnomad4 AMR

AF:

0.380

Gnomad4 ASJ

AF:

0.390

Gnomad4 EAS

AF:

0.255

Gnomad4 SAS

AF:

0.296

Gnomad4 FIN

AF:

0.446

Gnomad4 NFE

AF:

0.454

Gnomad4 OTH

AF:

0.399

Alfa

AF:

0.427

Hom.:

9704

Bravo

AF:

0.392

Asia WGS

AF:

0.298

AC:

1037

AN:

3478

EpiCase

AF:

0.458

EpiControl

AF:

0.455

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.48

DANN

Benign

0.54

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