rs585692

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001377.3(DYNC2H1):c.5718C>A(p.Thr1906Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 1,541,246 control chromosomes in the GnomAD database, including 661,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.94 ( 67723 hom., cov: 32)

Exomes 𝑓: 0.92 ( 593624 hom. )

Consequence

DYNC2H1
NM_001377.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.509

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 11-103176278-C-A is Benign according to our data. Variant chr11-103176278-C-A is described in ClinVar as [Benign]. Clinvar id is 167011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-103176278-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.509 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.972 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.5718C>A	p.Thr1906Thr	synonymous_variant	37/90	ENST00000650373.2	NP_001073932.1	Q8NCM8-2
DYNC2H1	NM_001377.3 linkuse as main transcript	c.5718C>A	p.Thr1906Thr	synonymous_variant	37/89	ENST00000375735.7	NP_001368.2	Q8NCM8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2 linkuse as main transcript	c.5718C>A	p.Thr1906Thr	synonymous_variant	37/90		NM_001080463.2	ENSP00000497174.1		Q8NCM8-2
DYNC2H1	ENST00000375735.7 linkuse as main transcript	c.5718C>A	p.Thr1906Thr	synonymous_variant	37/89	1	NM_001377.3	ENSP00000364887.2		Q8NCM8-1

Frequencies

GnomAD3 genomes

AF:

0.943

AC:

143403

AN:

152150

Hom.:

67652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.980

Gnomad AMI

AF:

0.971

Gnomad AMR

AF:

0.942

Gnomad ASJ

AF:

0.911

Gnomad EAS

AF:

0.873

Gnomad SAS

AF:

0.880

Gnomad FIN

AF:

0.976

Gnomad MID

AF:

0.864

Gnomad NFE

AF:

0.926

Gnomad OTH

AF:

0.938

GnomAD3 exomes

AF:

0.926

AC:

137631

AN:

148700

Hom.:

63844

AF XY:

0.921

AC XY:

72449

AN XY:

78652

show subpopulations

Gnomad AFR exome

AF:

0.981

Gnomad AMR exome

AF:

0.961

Gnomad ASJ exome

AF:

0.908

Gnomad EAS exome

AF:

0.865

Gnomad SAS exome

AF:

0.879

Gnomad FIN exome

AF:

0.971

Gnomad NFE exome

AF:

0.924

Gnomad OTH exome

AF:

0.916

GnomAD4 exome

AF:

0.924

AC:

1283516

AN:

1388978

Hom.:

593624

Cov.:

AF XY:

0.922

AC XY:

631398

AN XY:

684764

show subpopulations

Gnomad4 AFR exome

AF:

0.981

Gnomad4 AMR exome

AF:

0.959

Gnomad4 ASJ exome

AF:

0.912

Gnomad4 EAS exome

AF:

0.855

Gnomad4 SAS exome

AF:

0.880

Gnomad4 FIN exome

AF:

0.969

Gnomad4 NFE exome

AF:

0.925

Gnomad4 OTH exome

AF:

0.924

GnomAD4 genome

AF:

0.943

AC:

143533

AN:

152268

Hom.:

67723

Cov.:

AF XY:

0.942

AC XY:

70140

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.980

Gnomad4 AMR

AF:

0.942

Gnomad4 ASJ

AF:

0.911

Gnomad4 EAS

AF:

0.873

Gnomad4 SAS

AF:

0.881

Gnomad4 FIN

AF:

0.976

Gnomad4 NFE

AF:

0.926

Gnomad4 OTH

AF:

0.938

Alfa

AF:

0.931

Hom.:

40609

Bravo

AF:

0.943

Asia WGS

AF:

0.853

AC:

2964

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

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, 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	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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	Eurofins Ntd Llc (ga)	Apr 27, 2014	- -

Jeune thoracic dystrophy

Benign:2

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

Asphyxiating thoracic dystrophy 3

Benign:2

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. -

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

BayesDel_noAF

Benign

-0.27

CADD

Benign

1.8

DANN

Benign

0.60

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