rs2566913

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001377.3(DYNC2H1):ā€‹c.12096T>Cā€‹(p.Asp4032Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 1,589,806 control chromosomes in the GnomAD database, including 323,291 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.55 ( 24777 hom., cov: 32)
Exomes š‘“: 0.64 ( 298514 hom. )

Consequence

DYNC2H1
NM_001377.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.179
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant 11-103358299-T-C is Benign according to our data. Variant chr11-103358299-T-C is described in ClinVar as [Benign]. Clinvar id is 302117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-103358299-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.179 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DYNC2H1NM_001080463.2 linkuse as main transcriptc.12117T>C p.Asp4039Asp synonymous_variant 84/90 ENST00000650373.2 NP_001073932.1 Q8NCM8-2
DYNC2H1NM_001377.3 linkuse as main transcriptc.12096T>C p.Asp4032Asp synonymous_variant 83/89 ENST00000375735.7 NP_001368.2 Q8NCM8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DYNC2H1ENST00000650373.2 linkuse as main transcriptc.12117T>C p.Asp4039Asp synonymous_variant 84/90 NM_001080463.2 ENSP00000497174.1 Q8NCM8-2
DYNC2H1ENST00000375735.7 linkuse as main transcriptc.12096T>C p.Asp4032Asp synonymous_variant 83/891 NM_001377.3 ENSP00000364887.2 Q8NCM8-1

Frequencies

GnomAD3 genomes
AF:
0.549
AC:
83387
AN:
151878
Hom.:
24765
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.301
Gnomad AMI
AF:
0.646
Gnomad AMR
AF:
0.663
Gnomad ASJ
AF:
0.608
Gnomad EAS
AF:
0.513
Gnomad SAS
AF:
0.535
Gnomad FIN
AF:
0.643
Gnomad MID
AF:
0.615
Gnomad NFE
AF:
0.658
Gnomad OTH
AF:
0.580
GnomAD3 exomes
AF:
0.619
AC:
134827
AN:
217838
Hom.:
42979
AF XY:
0.617
AC XY:
72089
AN XY:
116846
show subpopulations
Gnomad AFR exome
AF:
0.287
Gnomad AMR exome
AF:
0.735
Gnomad ASJ exome
AF:
0.613
Gnomad EAS exome
AF:
0.508
Gnomad SAS exome
AF:
0.531
Gnomad FIN exome
AF:
0.663
Gnomad NFE exome
AF:
0.661
Gnomad OTH exome
AF:
0.638
GnomAD4 exome
AF:
0.640
AC:
920191
AN:
1437810
Hom.:
298514
Cov.:
37
AF XY:
0.638
AC XY:
454675
AN XY:
712966
show subpopulations
Gnomad4 AFR exome
AF:
0.276
Gnomad4 AMR exome
AF:
0.724
Gnomad4 ASJ exome
AF:
0.604
Gnomad4 EAS exome
AF:
0.532
Gnomad4 SAS exome
AF:
0.530
Gnomad4 FIN exome
AF:
0.662
Gnomad4 NFE exome
AF:
0.662
Gnomad4 OTH exome
AF:
0.608
GnomAD4 genome
AF:
0.549
AC:
83427
AN:
151996
Hom.:
24777
Cov.:
32
AF XY:
0.549
AC XY:
40787
AN XY:
74302
show subpopulations
Gnomad4 AFR
AF:
0.301
Gnomad4 AMR
AF:
0.663
Gnomad4 ASJ
AF:
0.608
Gnomad4 EAS
AF:
0.512
Gnomad4 SAS
AF:
0.535
Gnomad4 FIN
AF:
0.643
Gnomad4 NFE
AF:
0.658
Gnomad4 OTH
AF:
0.577
Alfa
AF:
0.637
Hom.:
40122
Bravo
AF:
0.544
Asia WGS
AF:
0.533
AC:
1854
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:5
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2016This 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 providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 28, 2016Variant 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 -
Jeune thoracic dystrophy Benign:2
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Asphyxiating thoracic dystrophy 3 Benign:2
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 30, 2021- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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. -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
CADD
Benign
3.9
DANN
Benign
0.86

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.

Other links and lift over

dbSNP: rs2566913; hg19: chr11-103229027; COSMIC: COSV62089585; API