11-103158787-A-G

Variant names:

Variant summary

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

The NM_001377.3(DYNC2H1):c.4238A>G(p.Lys1413Arg) variant causes a missense change. The variant allele was found at a frequency of 0.718 in 1,467,266 control chromosomes in the GnomAD database, including 381,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 35258 hom., cov: 32)

Exomes 𝑓: 0.72 ( 345999 hom. )

Consequence

DYNC2H1
NM_001377.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 3.90

Variant links:

Genes affected

DYNC2H1 (HGNC:2962): (dynein cytoplasmic 2 heavy chain 1) This gene encodes a large cytoplasmic dynein protein that is involved in retrograde transport in the cilium and has a role in intraflagellar transport, a process required for ciliary/flagellar assembly. Mutations in this gene cause a heterogeneous spectrum of conditions related to altered primary cilium function and often involve polydactyly, abnormal skeletogenesis, and polycystic kidneys. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jan 2010]

DYNC2H1 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=1.3857141E-6).

BP6

Variant 11-103158787-A-G is Benign according to our data. Variant chr11-103158787-A-G is described in ClinVar as [Benign]. Clinvar id is 196009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-103158787-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2 link	c.4238A>G	p.Lys1413Arg	missense_variant	Exon 27 of 90	ENST00000650373.2	NP_001073932.1	Q8NCM8-2
DYNC2H1	NM_001377.3 link	c.4238A>G	p.Lys1413Arg	missense_variant	Exon 27 of 89	ENST00000375735.7	NP_001368.2	Q8NCM8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2 link	c.4238A>G	p.Lys1413Arg	missense_variant	Exon 27 of 90		NM_001080463.2	ENSP00000497174.1		Q8NCM8-2
DYNC2H1	ENST00000375735.7 link	c.4238A>G	p.Lys1413Arg	missense_variant	Exon 27 of 89	1	NM_001377.3	ENSP00000364887.2		Q8NCM8-1

Frequencies

GnomAD3 genomes

AF:

0.672

AC:

102059

AN:

151798

Hom.:

35234

Cov.:

show subpopulations

Gnomad AFR

AF:

0.492

Gnomad AMI

AF:

0.686

Gnomad AMR

AF:

0.760

Gnomad ASJ

AF:

0.778

Gnomad EAS

AF:

0.768

Gnomad SAS

AF:

0.720

Gnomad FIN

AF:

0.756

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.733

Gnomad OTH

AF:

0.680

GnomAD3 exomes

AF:

0.739

AC:

102345

AN:

138432

Hom.:

38255

AF XY:

0.741

AC XY:

53717

AN XY:

72466

show subpopulations

Gnomad AFR exome

AF:

0.487

Gnomad AMR exome

AF:

0.806

Gnomad ASJ exome

AF:

0.776

Gnomad EAS exome

AF:

0.767

Gnomad SAS exome

AF:

0.725

Gnomad FIN exome

AF:

0.766

Gnomad NFE exome

AF:

0.738

Gnomad OTH exome

AF:

0.742

GnomAD4 exome

AF:

0.723

AC:

950690

AN:

1315350

Hom.:

345999

Cov.:

AF XY:

0.723

AC XY:

470161

AN XY:

649918

show subpopulations

Gnomad4 AFR exome

AF:

0.478

Gnomad4 AMR exome

AF:

0.795

Gnomad4 ASJ exome

AF:

0.779

Gnomad4 EAS exome

AF:

0.722

Gnomad4 SAS exome

AF:

0.720

Gnomad4 FIN exome

AF:

0.761

Gnomad4 NFE exome

AF:

0.725

Gnomad4 OTH exome

AF:

0.716

GnomAD4 genome

AF:

0.672

AC:

102123

AN:

151916

Hom.:

35258

Cov.:

AF XY:

0.675

AC XY:

50131

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.492

Gnomad4 AMR

AF:

0.760

Gnomad4 ASJ

AF:

0.778

Gnomad4 EAS

AF:

0.768

Gnomad4 SAS

AF:

0.721

Gnomad4 FIN

AF:

0.756

Gnomad4 NFE

AF:

0.733

Gnomad4 OTH

AF:

0.680

Alfa

AF:

0.724

Hom.:

80278

Bravo

AF:

0.666

TwinsUK

AF:

0.732

AC:

2715

ALSPAC

AF:

0.724

AC:

2792

ESP6500AA

AF:

0.513

AC:

1736

ESP6500EA

AF:

0.742

AC:

5720

ExAC

AF:

0.655

AC:

48854

Asia WGS

AF:

0.702

AC:

2430

AN:

3458

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Jun 13, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 28, 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 -

Asphyxiating thoracic dystrophy 3

Benign:3

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jeune thoracic dystrophy

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

0.088

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;T;.;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.76

.;T;.;T

MetaRNN

Benign

0.0000014

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.8

L;L;L;L

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.8

N;.;.;N

REVEL

Benign

0.19

Sift

Benign

0.31

T;.;.;T

Sift4G

Benign

0.28

T;.;.;T

Polyphen

0.33

B;B;P;P

Vest4

0.049

MPC

0.093

ClinPred

0.018

GERP RS

5.8

Varity_R

0.16

gMVP

0.48

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