Variant 17-7734471-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_020877.5(DNAH2):c.741C>T(p.Thr247=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 1,613,722 control chromosomes in the GnomAD database, including 630 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 0.014 ( 46 hom., cov: 31)

Exomes 𝑓: 0.016 ( 584 hom. )

Consequence

DNAH2
NM_020877.5 splice_region, synonymous

Scores

Splicing: ADA: 0.0002104

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0650

Variant links:

Genes affected

DNAH2 (HGNC:2948): (dynein axonemal heavy chain 2) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. The axonemal dyneins, found in cilia and flagella, are components of the outer and inner dynein arms attached to the peripheral microtubule doublets. DNAH2 is an axonemal inner arm dynein heavy chain (Chapelin et al., 1997 [PubMed 9256245]).[supplied by OMIM, Mar 2008]

DNAH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 17-7734471-C-T is Benign according to our data. Variant chr17-7734471-C-T is described in ClinVar as [Benign]. Clinvar id is 3055611.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.065 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.079 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH2	NM_020877.5 linkuse as main transcript	c.741C>T	p.Thr247=	splice_region_variant, synonymous_variant	7/86	ENST00000572933.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH2	ENST00000572933.6 linkuse as main transcript	c.741C>T	p.Thr247=	splice_region_variant, synonymous_variant	7/86	2	NM_020877.5	P1	Q9P225-1
DNAH2	ENST00000570791.5 linkuse as main transcript	c.741C>T	p.Thr247=	splice_region_variant, synonymous_variant	7/14	1			Q9P225-3
DNAH2	ENST00000389173.6 linkuse as main transcript	c.741C>T	p.Thr247=	splice_region_variant, synonymous_variant	6/85	2		P1	Q9P225-1

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2170

AN:

151784

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00286

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0108

Gnomad ASJ

AF:

0.0265

Gnomad EAS

AF:

0.0591

Gnomad SAS

AF:

0.0856

Gnomad FIN

AF:

0.0383

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00931

Gnomad OTH

AF:

0.0149

GnomAD3 exomes

AF:

0.0266

AC:

6684

AN:

251110

Hom.:

223

AF XY:

0.0292

AC XY:

3965

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.00326

Gnomad AMR exome

AF:

0.0200

Gnomad ASJ exome

AF:

0.0283

Gnomad EAS exome

AF:

0.0584

Gnomad SAS exome

AF:

0.0867

Gnomad FIN exome

AF:

0.0332

Gnomad NFE exome

AF:

0.00918

Gnomad OTH exome

AF:

0.0274

GnomAD4 exome

AF:

0.0163

AC:

23780

AN:

1461820

Hom.:

584

Cov.:

AF XY:

0.0182

AC XY:

13271

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00347

Gnomad4 AMR exome

AF:

0.0185

Gnomad4 ASJ exome

AF:

0.0295

Gnomad4 EAS exome

AF:

0.0509

Gnomad4 SAS exome

AF:

0.0835

Gnomad4 FIN exome

AF:

0.0317

Gnomad4 NFE exome

AF:

0.00860

Gnomad4 OTH exome

AF:

0.0227

GnomAD4 genome

AF:

0.0144

AC:

2184

AN:

151902

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1271

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.00285

Gnomad4 AMR

AF:

0.0108

Gnomad4 ASJ

AF:

0.0265

Gnomad4 EAS

AF:

0.0595

Gnomad4 SAS

AF:

0.0858

Gnomad4 FIN

AF:

0.0383

Gnomad4 NFE

AF:

0.00931

Gnomad4 OTH

AF:

0.0210

Alfa

AF:

0.0131

Hom.:

130

Bravo

AF:

0.0108

Asia WGS

AF:

0.113

AC:

394

AN:

3478

EpiCase

AF:

0.0106

EpiControl

AF:

0.00931

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DNAH2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 18, 2019

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

-0.31

CADD

Benign

8.6

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00021

dbscSNV1_RF

Benign

0.0

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