Variant rs2251644 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001376.5(DYNC1H1):c.4396-25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,613,774 control chromosomes in the GnomAD database, including 20,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4411 hom., cov: 32)

Exomes 𝑓: 0.13 ( 15947 hom. )

Consequence

DYNC1H1
NM_001376.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.28

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 14-102001510-A-G is Benign according to our data. Variant chr14-102001510-A-G is described in ClinVar as [Benign]. Clinvar id is 674076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC1H1	NM_001376.5 linkuse as main transcript	c.4396-25A>G		intron_variant		ENST00000360184.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC1H1	ENST00000360184.10 linkuse as main transcript	c.4396-25A>G		intron_variant		1	NM_001376.5	P1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31491

AN:

151914

Hom.:

4399

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.203

GnomAD3 exomes

AF:

0.173

AC:

43525

AN:

251418

Hom.:

4744

AF XY:

0.168

AC XY:

22836

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.394

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.179

Gnomad EAS exome

AF:

0.288

Gnomad SAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.0964

Gnomad NFE exome

AF:

0.114

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.134

AC:

195251

AN:

1461744

Hom.:

15947

Cov.:

AF XY:

0.135

AC XY:

98311

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.399

Gnomad4 AMR exome

AF:

0.211

Gnomad4 ASJ exome

AF:

0.176

Gnomad4 EAS exome

AF:

0.274

Gnomad4 SAS exome

AF:

0.226

Gnomad4 FIN exome

AF:

0.102

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.153

GnomAD4 genome

AF:

0.208

AC:

31554

AN:

152030

Hom.:

4411

Cov.:

AF XY:

0.206

AC XY:

15310

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.390

Gnomad4 AMR

AF:

0.196

Gnomad4 ASJ

AF:

0.169

Gnomad4 EAS

AF:

0.275

Gnomad4 SAS

AF:

0.238

Gnomad4 FIN

AF:

0.102

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.202

Alfa

AF:

0.152

Hom.:

713

Bravo

AF:

0.222

Asia WGS

AF:

0.262

AC:

909

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

Charcot-Marie-Tooth disease axonal type 2O

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

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. -

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

-0.95

CADD

Benign

0.0070

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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