rs117178504

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001377.3(DYNC2H1):c.10864C>A(p.Arg3622Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,607,294 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 6 hom., cov: 32)

Exomes 𝑓: 0.011 ( 105 hom. )

Consequence

DYNC2H1
NM_001377.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.170

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.21).

BP6

Variant 11-103283059-C-A is Benign according to our data. Variant chr11-103283059-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 220090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-103283059-C-A is described in Lovd as [Benign]. Variant chr11-103283059-C-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.17 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00764 (1161/152062) while in subpopulation AMR AF= 0.0131 (200/15254). AF 95% confidence interval is 0.0116. There are 6 homozygotes in gnomad4. There are 519 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2 link	c.10885C>A	p.Arg3629Arg	synonymous_variant	Exon 74 of 90	ENST00000650373.2	NP_001073932.1	Q8NCM8-2
DYNC2H1	NM_001377.3 link	c.10864C>A	p.Arg3622Arg	synonymous_variant	Exon 73 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.10885C>A	p.Arg3629Arg	synonymous_variant	Exon 74 of 90		NM_001080463.2	ENSP00000497174.1		Q8NCM8-2
DYNC2H1	ENST00000375735.7 link	c.10864C>A	p.Arg3622Arg	synonymous_variant	Exon 73 of 89	1	NM_001377.3	ENSP00000364887.2		Q8NCM8-1

Frequencies

GnomAD3 genomes

AF:

0.00764

AC:

1161

AN:

151942

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0131

Gnomad ASJ

AF:

0.00866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00699

AC:

1722

AN:

246432

Hom.:

AF XY:

0.00688

AC XY:

920

AN XY:

133790

show subpopulations

Gnomad AFR exome

AF:

0.00254

Gnomad AMR exome

AF:

0.00798

Gnomad ASJ exome

AF:

0.00911

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000729

Gnomad FIN exome

AF:

0.00210

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00907

GnomAD4 exome

AF:

0.0109

AC:

15878

AN:

1455232

Hom.:

105

Cov.:

AF XY:

0.0105

AC XY:

7577

AN XY:

723560

show subpopulations

Gnomad4 AFR exome

AF:

0.00156

Gnomad4 AMR exome

AF:

0.00934

Gnomad4 ASJ exome

AF:

0.0101

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000459

Gnomad4 FIN exome

AF:

0.00286

Gnomad4 NFE exome

AF:

0.0129

Gnomad4 OTH exome

AF:

0.0108

GnomAD4 genome

AF:

0.00764

AC:

1161

AN:

152062

Hom.:

Cov.:

AF XY:

0.00698

AC XY:

519

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00284

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.00866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.0112

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00872

Hom.:

Bravo

AF:

0.00914

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Feb 08, 2018

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. -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 08, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DYNC2H1: BP4, BP7, BS1, BS2 -

Jeune thoracic dystrophy

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Asphyxiating thoracic dystrophy 3

Benign:1

Nov 09, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.21

CADD

Benign

6.0

DANN

Benign

0.75

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