Variant 14-102030015-C-A 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.9762+77C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,610,468 control chromosomes in the GnomAD database, including 49,006 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 11694 hom., cov: 31)

Exomes 𝑓: 0.21 ( 37312 hom. )

Consequence

DYNC1H1
NM_001376.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.04

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=-0.88).

BP6

Variant 14-102030015-C-A is Benign according to our data. Variant chr14-102030015-C-A is described in ClinVar as [Benign]. Clinvar id is 674055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 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.9762+77C>A		intron_variant		ENST00000360184.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC1H1	ENST00000360184.10 linkuse as main transcript	c.9762+77C>A		intron_variant		1	NM_001376.5	P1

Frequencies

GnomAD3 genomes

AF:

0.336

AC:

50922

AN:

151568

Hom.:

11658

Cov.:

show subpopulations

Gnomad AFR

AF:

0.661

Gnomad AMI

AF:

0.0960

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.273

Gnomad SAS

AF:

0.262

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.274

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.333

GnomAD4 exome

AF:

0.211

AC:

307760

AN:

1458782

Hom.:

37312

Cov.:

AF XY:

0.211

AC XY:

152760

AN XY:

725654

show subpopulations

Gnomad4 AFR exome

AF:

0.686

Gnomad4 AMR exome

AF:

0.270

Gnomad4 ASJ exome

AF:

0.242

Gnomad4 EAS exome

AF:

0.272

Gnomad4 SAS exome

AF:

0.256

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.187

Gnomad4 OTH exome

AF:

0.237

GnomAD4 genome

AF:

0.336

AC:

51019

AN:

151686

Hom.:

11694

Cov.:

AF XY:

0.331

AC XY:

24542

AN XY:

74108

show subpopulations

Gnomad4 AFR

AF:

0.662

Gnomad4 AMR

AF:

0.274

Gnomad4 ASJ

AF:

0.241

Gnomad4 EAS

AF:

0.274

Gnomad4 SAS

AF:

0.262

Gnomad4 FIN

AF:

0.211

Gnomad4 NFE

AF:

0.190

Gnomad4 OTH

AF:

0.330

Alfa

AF:

0.233

Hom.:

2728

Bravo

AF:

0.356

Asia WGS

AF:

0.283

AC:

983

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.2

DANN

Benign

0.34

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