11-103287549-C-T

Position:

chr11-103287549-C-T

Variant summary

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

The NM_001377.3(DYNC2H1):c.11039C>T(p.Ala3680Val) variant causes a missense change. The variant allele was found at a frequency of 0.346 in 1,603,654 control chromosomes in the GnomAD database, including 98,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7180 hom., cov: 32)

Exomes 𝑓: 0.35 ( 91575 hom. )

Consequence

DYNC2H1
NM_001377.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 6.03

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:

ENSG00000285878 (HGNC:):

ENSG00000285878 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=0.0032462478).

BP6

Variant 11-103287549-C-T is Benign according to our data. Variant chr11-103287549-C-T is described in ClinVar as [Benign]. Clinvar id is 302107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-103287549-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2 link	c.11060C>T	p.Ala3687Val	missense_variant	76/90	ENST00000650373.2	NP_001073932.1	Q8NCM8-2
DYNC2H1	NM_001377.3 link	c.11039C>T	p.Ala3680Val	missense_variant	75/89	ENST00000375735.7	NP_001368.2	Q8NCM8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2 link	c.11060C>T	p.Ala3687Val	missense_variant	76/90		NM_001080463.2	ENSP00000497174.1		Q8NCM8-2
DYNC2H1	ENST00000375735.7 link	c.11039C>T	p.Ala3680Val	missense_variant	75/89	1	NM_001377.3	ENSP00000364887.2		Q8NCM8-1

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

45696

AN:

151842

Hom.:

7174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.422

Gnomad AMR

AF:

0.271

Gnomad ASJ

AF:

0.284

Gnomad EAS

AF:

0.287

Gnomad SAS

AF:

0.390

Gnomad FIN

AF:

0.351

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.358

Gnomad OTH

AF:

0.301

GnomAD3 exomes

AF:

0.319

AC:

77790

AN:

244088

Hom.:

13042

AF XY:

0.328

AC XY:

43478

AN XY:

132410

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.221

Gnomad ASJ exome

AF:

0.283

Gnomad EAS exome

AF:

0.279

Gnomad SAS exome

AF:

0.395

Gnomad FIN exome

AF:

0.334

Gnomad NFE exome

AF:

0.352

Gnomad OTH exome

AF:

0.325

GnomAD4 exome

AF:

0.351

AC:

509918

AN:

1451694

Hom.:

91575

Cov.:

AF XY:

0.353

AC XY:

254978

AN XY:

721994

show subpopulations

Gnomad4 AFR exome

AF:

0.195

Gnomad4 AMR exome

AF:

0.232

Gnomad4 ASJ exome

AF:

0.294

Gnomad4 EAS exome

AF:

0.290

Gnomad4 SAS exome

AF:

0.400

Gnomad4 FIN exome

AF:

0.335

Gnomad4 NFE exome

AF:

0.362

Gnomad4 OTH exome

AF:

0.346

GnomAD4 genome

AF:

0.301

AC:

45731

AN:

151960

Hom.:

7180

Cov.:

AF XY:

0.302

AC XY:

22429

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.271

Gnomad4 ASJ

AF:

0.284

Gnomad4 EAS

AF:

0.288

Gnomad4 SAS

AF:

0.389

Gnomad4 FIN

AF:

0.351

Gnomad4 NFE

AF:

0.357

Gnomad4 OTH

AF:

0.302

Alfa

AF:

0.340

Hom.:

22752

Bravo

AF:

0.285

TwinsUK

AF:

0.368

AC:

1364

ALSPAC

AF:

0.356

AC:

1371

ESP6500AA

AF:

0.204

AC:

742

ESP6500EA

AF:

0.352

AC:

2869

ExAC

AF:

0.325

AC:

39276

Asia WGS

AF:

0.324

AC:

1126

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 29, 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	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	-	- -

Asphyxiating thoracic dystrophy 3

Benign:3

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	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

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

0.25

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T;.;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.79

.;T;.;T

MetaRNN

Benign

0.0032

T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.3

M;M;.;.

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.0

D;.;.;D

REVEL

Benign

0.23

Sift

Benign

0.11

T;.;.;T

Sift4G

Benign

0.12

T;.;.;T

Polyphen

0.60

P;P;P;P

Vest4

0.29

MPC

0.080

ClinPred

0.015

GERP RS

5.8

Varity_R

0.49

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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