rs3818188

Positions:

Variant summary

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

The NM_001376.5(DYNC1H1):c.624G>A(p.Pro208Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,614,016 control chromosomes in the GnomAD database, including 33,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 3050 hom., cov: 32)

Exomes 𝑓: 0.19 ( 30731 hom. )

Consequence

DYNC1H1
NM_001376.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:17

Conservation

PhyloP100: -0.372

Variant links:

Genes affected

DYNC1H1 (HGNC:2961): (dynein cytoplasmic 1 heavy chain 1) Dyneins are a group of microtubule-activated ATPases that function as molecular motors. They are divided into two subgroups of axonemal and cytoplasmic dyneins. The cytoplasmic dyneins function in intracellular motility, including retrograde axonal transport, protein sorting, organelle movement, and spindle dynamics. Molecules of conventional cytoplasmic dynein are comprised of 2 heavy chain polypeptides and a number of intermediate and light chains.This gene encodes a member of the cytoplasmic dynein heavy chain family. [provided by RefSeq, Oct 2008]

DYNC1H1 links:

DYNC1H1 (HGNC:):

DYNC1H1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 14-101979824-G-A is Benign according to our data. Variant chr14-101979824-G-A is described in ClinVar as [Benign]. Clinvar id is 128939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-101979824-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.372 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC1H1	NM_001376.5 linkuse as main transcript	c.624G>A	p.Pro208Pro	synonymous_variant	4/78	ENST00000360184.10	NP_001367.2	Q14204

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC1H1	ENST00000360184.10 linkuse as main transcript	c.624G>A	p.Pro208Pro	synonymous_variant	4/78	1	NM_001376.5	ENSP00000348965.4		Q14204

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

26073

AN:

152042

Hom.:

3047

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0436

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.465

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.190

GnomAD3 exomes

AF:

0.221

AC:

55636

AN:

251416

Hom.:

7665

AF XY:

0.215

AC XY:

29145

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0406

Gnomad AMR exome

AF:

0.362

Gnomad ASJ exome

AF:

0.290

Gnomad EAS exome

AF:

0.455

Gnomad SAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.188

Gnomad OTH exome

AF:

0.220

GnomAD4 exome

AF:

0.193

AC:

281766

AN:

1461856

Hom.:

30731

Cov.:

AF XY:

0.191

AC XY:

138900

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0370

Gnomad4 AMR exome

AF:

0.353

Gnomad4 ASJ exome

AF:

0.292

Gnomad4 EAS exome

AF:

0.496

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.197

Gnomad4 NFE exome

AF:

0.181

Gnomad4 OTH exome

AF:

0.203

GnomAD4 genome

AF:

0.171

AC:

26086

AN:

152160

Hom.:

3050

Cov.:

AF XY:

0.178

AC XY:

13259

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0435

Gnomad4 AMR

AF:

0.298

Gnomad4 ASJ

AF:

0.300

Gnomad4 EAS

AF:

0.464

Gnomad4 SAS

AF:

0.147

Gnomad4 FIN

AF:

0.200

Gnomad4 NFE

AF:

0.187

Gnomad4 OTH

AF:

0.196

Alfa

AF:

0.184

Hom.:

4646

Bravo

AF:

0.175

Asia WGS

AF:

0.302

AC:

1046

AN:

3478

EpiCase

AF:

0.181

EpiControl

AF:

0.183

ClinVar

Significance: Benign

Submissions summary: Benign:17

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 20, 2014	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, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 14, 2015	- -
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	PreventionGenetics, part of Exact Sciences	-	- -
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, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 25, 2013	- -

Charcot-Marie-Tooth disease axonal type 2O

Benign:3

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

Autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autosomal dominant cerebellar ataxia

Benign:1

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. -

Intellectual disability, autosomal dominant 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.1

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