NM_020877.5:c.12303A>T

Variant names:

Variant summary

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

The NM_020877.5(DNAH2):c.12303A>T(p.Leu4101Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0235 in 1,614,068 control chromosomes in the GnomAD database, including 618 homozygotes. In-silico tool predicts 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 ( 556 hom. )

Consequence

DNAH2
NM_020877.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.05

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 (MetaRNN=0.0041172802).

BP6

Variant 17-7831158-A-T is Benign according to our data. Variant chr17-7831158-A-T is described in ClinVar as [Benign]. Clinvar id is 402715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH2	NM_020877.5 link	c.12303A>T	p.Leu4101Phe	missense_variant	Exon 80 of 86	ENST00000572933.6	NP_065928.2	Q9P225-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH2	ENST00000572933.6 link	c.12303A>T	p.Leu4101Phe	missense_variant	Exon 80 of 86	2	NM_020877.5	ENSP00000458355.1	Q9P225-1
DNAH2	ENST00000389173.6 link	c.12303A>T	p.Leu4101Phe	missense_variant	Exon 79 of 85	2		ENSP00000373825.2	Q9P225-1
DNAH2	ENST00000575105.1 link	c.3150A>T	p.Leu1050Phe	missense_variant	Exon 21 of 23	5		ENSP00000461726.1	I3L520

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3513

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00727

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0347

Gnomad ASJ

AF:

0.0591

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00705

Gnomad FIN

AF:

0.0514

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0255

Gnomad OTH

AF:

0.0440

GnomAD3 exomes

AF:

0.0245

AC:

6161

AN:

251444

Hom.:

118

AF XY:

0.0247

AC XY:

3363

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00634

Gnomad AMR exome

AF:

0.0201

Gnomad ASJ exome

AF:

0.0602

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00817

Gnomad FIN exome

AF:

0.0505

Gnomad NFE exome

AF:

0.0279

Gnomad OTH exome

AF:

0.0386

GnomAD4 exome

AF:

0.0235

AC:

34421

AN:

1461848

Hom.:

556

Cov.:

AF XY:

0.0235

AC XY:

17121

AN XY:

727216

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:

0.00883

Gnomad4 FIN exome

AF:

0.0496

Gnomad4 NFE exome

AF:

0.0235

Gnomad4 OTH exome

AF:

0.0293

GnomAD4 genome

AF:

0.0231

AC:

3514

AN:

152220

Hom.:

Cov.:

AF XY:

0.0244

AC XY:

1815

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00727

Gnomad4 AMR

AF:

0.0346

Gnomad4 ASJ

AF:

0.0591

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.00684

Gnomad4 FIN

AF:

0.0514

Gnomad4 NFE

AF:

0.0255

Gnomad4 OTH

AF:

0.0436

Alfa

AF:

0.0285

Hom.:

Bravo

AF:

0.0212

TwinsUK

AF:

0.0218

AC:

ALSPAC

AF:

0.0254

AC:

ESP6500AA

AF:

0.00658

AC:

ESP6500EA

AF:

0.0295

AC:

254

ExAC

AF:

0.0232

AC:

2816

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.0345

EpiControl

AF:

0.0338

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

DNAH2-related disorder

Benign:1

May 13, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;T;.

Eigen

Benign

0.090

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.85

.;T;T

MetaRNN

Benign

0.0041

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.7

.;N;.

REVEL

Benign

0.083

Sift

Benign

0.050

.;D;.

Sift4G

Uncertain

0.055

.;.;T

Polyphen

0.41

B;B;.

Vest4

0.097

MutPred

0.34

Loss of ubiquitination at K4096 (P = 0.0992);Loss of ubiquitination at K4096 (P = 0.0992);.;

MPC

0.50

ClinPred

0.019

GERP RS

3.6

Varity_R

0.40

gMVP

0.14

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