rs79350244

Positions:

chr17-7830796-A-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_020877.5(DNAH2):c.12184A>C(p.Ile4062Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0236 in 1,614,040 control chromosomes in the GnomAD database, including 621 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 62 hom., cov: 32)

Exomes 𝑓: 0.024 ( 559 hom. )

Consequence

DNAH2
NM_020877.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.60

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 -19 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DNAH2. . Gene score misZ 1.883 (greater than the threshold 3.09). Trascript score misZ 4.8003 (greater than threshold 3.09). GenCC has associacion of gene with spermatogenic failure 45.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043467283).

BP6

Variant 17-7830796-A-C is Benign according to our data. Variant chr17-7830796-A-C is described in ClinVar as [Benign]. Clinvar id is 402714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7830796-A-C is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH2	NM_020877.5 linkuse as main transcript	c.12184A>C	p.Ile4062Leu	missense_variant	79/86	ENST00000572933.6	NP_065928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH2	ENST00000572933.6 linkuse as main transcript	c.12184A>C	p.Ile4062Leu	missense_variant	79/86	2	NM_020877.5	ENSP00000458355	P1	Q9P225-1
DNAH2	ENST00000389173.6 linkuse as main transcript	c.12184A>C	p.Ile4062Leu	missense_variant	78/85	2		ENSP00000373825	P1	Q9P225-1
DNAH2	ENST00000575105.1 linkuse as main transcript	c.3031A>C	p.Ile1011Leu	missense_variant	20/23	5		ENSP00000461726

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3517

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00727

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0348

Gnomad ASJ

AF:

0.0590

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.00704

Gnomad FIN

AF:

0.0514

Gnomad MID

AF:

0.0987

Gnomad NFE

AF:

0.0255

Gnomad OTH

AF:

0.0439

GnomAD3 exomes

AF:

0.0246

AC:

6170

AN:

251170

Hom.:

119

AF XY:

0.0248

AC XY:

3373

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.00635

Gnomad AMR exome

AF:

0.0202

Gnomad ASJ exome

AF:

0.0603

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00820

Gnomad FIN exome

AF:

0.0505

Gnomad NFE exome

AF:

0.0280

Gnomad OTH exome

AF:

0.0389

GnomAD4 exome

AF:

0.0236

AC:

34511

AN:

1461770

Hom.:

559

Cov.:

AF XY:

0.0236

AC XY:

17169

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00541

Gnomad4 AMR exome

AF:

0.0221

Gnomad4 ASJ exome

AF:

0.0568

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00890

Gnomad4 FIN exome

AF:

0.0496

Gnomad4 NFE exome

AF:

0.0235

Gnomad4 OTH exome

AF:

0.0293

GnomAD4 genome

AF:

0.0231

AC:

3518

AN:

152270

Hom.:

Cov.:

AF XY:

0.0244

AC XY:

1819

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00727

Gnomad4 AMR

AF:

0.0347

Gnomad4 ASJ

AF:

0.0590

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00684

Gnomad4 FIN

AF:

0.0514

Gnomad4 NFE

AF:

0.0255

Gnomad4 OTH

AF:

0.0435

Alfa

AF:

0.0271

Hom.:

120

Bravo

AF:

0.0213

TwinsUK

AF:

0.0218

AC:

ALSPAC

AF:

0.0259

AC:

100

ESP6500AA

AF:

0.00658

AC:

ESP6500EA

AF:

0.0298

AC:

256

ExAC

AF:

0.0233

AC:

2824

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.0345

EpiControl

AF:

0.0340

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

DNAH2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 13, 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). -

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 -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.036

T;T;.

Eigen

Benign

-0.014

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.76

.;T;D

MetaRNN

Benign

0.0043

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.23

N;N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.1

.;N;.

REVEL

Benign

0.16

Sift

Benign

0.28

.;T;.

Sift4G

Benign

0.21

.;.;T

Polyphen

0.52

P;P;.

Vest4

0.29

MPC

0.80

ClinPred

0.011

GERP RS

5.8

Varity_R

0.44

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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