Variant rs872346 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020877.5(DNAH2):c.10169+3G>A 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 0.344 in 1,613,956 control chromosomes in the GnomAD database, including 103,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6908 hom., cov: 31)

Exomes 𝑓: 0.35 ( 96143 hom. )

Consequence

DNAH2
NM_020877.5 splice_donor_region, intron

Scores

Splicing: ADA: 0.00002793

Clinical Significance

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

Conservation

PhyloP100: -1.05

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 17-7817712-G-A is Benign according to our data. Variant chr17-7817712-G-A is described in ClinVar as [Benign]. Clinvar id is 402712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 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.10169+3G>A		splice_donor_region_variant, intron_variant		ENST00000572933.6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
DNAH2	ENST00000572933.6 linkuse as main transcript	c.10169+3G>A	splice_donor_region_variant, intron_variant	2	NM_020877.5	P1	Q9P225-1
DNAH2	ENST00000389173.6 linkuse as main transcript	c.10169+3G>A	splice_donor_region_variant, intron_variant	2		P1	Q9P225-1
DNAH2	ENST00000575105.1 linkuse as main transcript	c.1016+3G>A	splice_donor_region_variant, intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42068

AN:

151970

Hom.:

6902

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.378

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.0637

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.391

Gnomad OTH

AF:

0.311

GnomAD3 exomes

AF:

0.280

AC:

70247

AN:

251192

Hom.:

11693

AF XY:

0.286

AC XY:

38832

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.187

Gnomad ASJ exome

AF:

0.360

Gnomad EAS exome

AF:

0.0626

Gnomad SAS exome

AF:

0.163

Gnomad FIN exome

AF:

0.286

Gnomad NFE exome

AF:

0.387

Gnomad OTH exome

AF:

0.326

GnomAD4 exome

AF:

0.351

AC:

512761

AN:

1461866

Hom.:

96143

Cov.:

AF XY:

0.347

AC XY:

252292

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.193

Gnomad4 ASJ exome

AF:

0.362

Gnomad4 EAS exome

AF:

0.0681

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.285

Gnomad4 NFE exome

AF:

0.393

Gnomad4 OTH exome

AF:

0.331

GnomAD4 genome

AF:

0.277

AC:

42107

AN:

152090

Hom.:

6908

Cov.:

AF XY:

0.268

AC XY:

19939

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.356

Gnomad4 EAS

AF:

0.0639

Gnomad4 SAS

AF:

0.160

Gnomad4 FIN

AF:

0.280

Gnomad4 NFE

AF:

0.391

Gnomad4 OTH

AF:

0.310

Alfa

AF:

0.366

Hom.:

17756

Bravo

AF:

0.269

Asia WGS

AF:

0.124

AC:

430

AN:

3478

EpiCase

AF:

0.409

EpiControl

AF:

0.401

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 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 -

DNAH2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

-0.91

CADD

Benign

0.082

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000028

dbscSNV1_RF

Benign

0.036

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