rs589623

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001377.3(DYNC2H1):c.8612G>A(p.Arg2871Gln) variant causes a missense change. The variant allele was found at a frequency of 0.793 in 1,521,494 control chromosomes in the GnomAD database, including 480,082 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 43913 hom., cov: 32)

Exomes 𝑓: 0.80 ( 436169 hom. )

Consequence

DYNC2H1
NM_001377.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.41

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=2.285225E-6).

BP6

Variant 11-103211861-G-A is Benign according to our data. Variant chr11-103211861-G-A is described in ClinVar as [Benign]. Clinvar id is 302073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-103211861-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2 link	c.8612G>A	p.Arg2871Gln	missense_variant	Exon 54 of 90	ENST00000650373.2	NP_001073932.1	Q8NCM8-2
DYNC2H1	NM_001377.3 link	c.8612G>A	p.Arg2871Gln	missense_variant	Exon 54 of 89	ENST00000375735.7	NP_001368.2	Q8NCM8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DYNC2H1	ENST00000650373.2 link	c.8612G>A	p.Arg2871Gln	missense_variant	Exon 54 of 90		NM_001080463.2	ENSP00000497174.1	Q8NCM8-2
DYNC2H1	ENST00000375735.7 link	c.8612G>A	p.Arg2871Gln	missense_variant	Exon 54 of 89	1	NM_001377.3	ENSP00000364887.2	Q8NCM8-1
DYNC2H1	ENST00000334267.11 link	c.2205+77442G>A		intron_variant	Intron 15 of 19	1		ENSP00000334021.7	Q8NCM8-3
DYNC2H1	ENST00000533027.1 link	n.212G>A		non_coding_transcript_exon_variant	Exon 3 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.756

AC:

114756

AN:

151872

Hom.:

43869

Cov.:

show subpopulations

Gnomad AFR

AF:

0.621

Gnomad AMI

AF:

0.899

Gnomad AMR

AF:

0.835

Gnomad ASJ

AF:

0.846

Gnomad EAS

AF:

0.777

Gnomad SAS

AF:

0.772

Gnomad FIN

AF:

0.790

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.804

Gnomad OTH

AF:

0.779

GnomAD3 exomes

AF:

0.794

AC:

120667

AN:

152026

Hom.:

48240

AF XY:

0.795

AC XY:

63767

AN XY:

80228

show subpopulations

Gnomad AFR exome

AF:

0.603

Gnomad AMR exome

AF:

0.848

Gnomad ASJ exome

AF:

0.839

Gnomad EAS exome

AF:

0.767

Gnomad SAS exome

AF:

0.765

Gnomad FIN exome

AF:

0.802

Gnomad NFE exome

AF:

0.805

Gnomad OTH exome

AF:

0.806

GnomAD4 exome

AF:

0.797

AC:

1091217

AN:

1369504

Hom.:

436169

Cov.:

AF XY:

0.796

AC XY:

537112

AN XY:

674624

show subpopulations

Gnomad4 AFR exome

AF:

0.610

Gnomad4 AMR exome

AF:

0.847

Gnomad4 ASJ exome

AF:

0.848

Gnomad4 EAS exome

AF:

0.731

Gnomad4 SAS exome

AF:

0.766

Gnomad4 FIN exome

AF:

0.802

Gnomad4 NFE exome

AF:

0.804

Gnomad4 OTH exome

AF:

0.787

GnomAD4 genome

AF:

0.756

AC:

114855

AN:

151990

Hom.:

43913

Cov.:

AF XY:

0.756

AC XY:

56184

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.621

Gnomad4 AMR

AF:

0.835

Gnomad4 ASJ

AF:

0.846

Gnomad4 EAS

AF:

0.777

Gnomad4 SAS

AF:

0.774

Gnomad4 FIN

AF:

0.790

Gnomad4 NFE

AF:

0.804

Gnomad4 OTH

AF:

0.779

Alfa

AF:

0.799

Hom.:

101576

Bravo

AF:

0.754

TwinsUK

AF:

0.803

AC:

2979

ALSPAC

AF:

0.804

AC:

3099

ESP6500AA

AF:

0.630

AC:

2258

ESP6500EA

AF:

0.810

AC:

6501

ExAC

AF:

0.741

AC:

70849

Asia WGS

AF:

0.734

AC:

2544

AN:

3462

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 03, 2016

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. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Asphyxiating thoracic dystrophy 3

Benign:3

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jeune thoracic dystrophy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Short rib-polydactyly syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.093

T;T;.;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.81

.;T;.;T

MetaRNN

Benign

0.0000023

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.61

N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.7

N;.;.;N

REVEL

Benign

0.099

Sift

Benign

0.23

T;.;.;T

Sift4G

Benign

0.30

T;.;.;T

Polyphen

0.72

P;P;B;B

Vest4

0.049

MPC

0.084

ClinPred

0.017

GERP RS

5.8

Varity_R

0.17

gMVP

0.15

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