chr11-103158787-A-G

Position:

chr11-103158787-A-G

Variant summary

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

The ENST00000375735.7(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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar.

Frequency

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

Exomes 𝑓: 0.72 ( 345999 hom. )

Consequence

DYNC2H1
ENST00000375735.7 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/exons	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2 linkuse as main transcript	c.4238A>G	p.Lys1413Arg	missense_variant	27/90	ENST00000650373.2	NP_001073932.1
DYNC2H1	NM_001377.3 linkuse as main transcript	c.4238A>G	p.Lys1413Arg	missense_variant	27/89	ENST00000375735.7	NP_001368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2 linkuse as main transcript	c.4238A>G	p.Lys1413Arg	missense_variant	27/90		NM_001080463.2	ENSP00000497174	A1	Q8NCM8-2
DYNC2H1	ENST00000375735.7 linkuse as main transcript	c.4238A>G	p.Lys1413Arg	missense_variant	27/89	1	NM_001377.3	ENSP00000364887	P3	Q8NCM8-1
DYNC2H1	ENST00000334267.11 linkuse as main transcript	c.2205+24368A>G		intron_variant		1		ENSP00000334021		Q8NCM8-3
DYNC2H1	ENST00000649323.1 linkuse as main transcript	c.*1783A>G		3_prime_UTR_variant, NMD_transcript_variant	25/51			ENSP00000497581

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

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 13, 2014	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 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 -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2016	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. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Asphyxiating thoracic dystrophy 3

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

Jeune thoracic dystrophy

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

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

0.088

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

MutationTaster

Benign

0.020

P;P;P

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