rs144444098

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_018051.5(DYNC2I1):c.1370C>A(p.Ser457Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000322 in 1,613,598 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

DYNC2I1
NM_018051.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.04

Variant links:

Genes affected

DYNC2I1 (HGNC:21862): (dynein 2 intermediate chain 1) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD) and may facilitate the formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes including cell cycle progression, signal transduction, apoptosis, and gene regulation. The encoded protein contains four WD repeats and may play a role in the formation of cilia. Mutations in this gene have been associated with short-rib polydactyly and Jeune syndromes. [provided by RefSeq, Mar 2014]

DYNC2I1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0068127513).

BP6

Variant 7-158906001-C-A is Benign according to our data. Variant chr7-158906001-C-A is described in ClinVar as [Benign]. Clinvar id is 541524.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00166 (253/152276) while in subpopulation AFR AF= 0.00551 (229/41546). AF 95% confidence interval is 0.00493. There are 1 homozygotes in gnomad4. There are 113 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2I1	NM_018051.5 link	c.1370C>A	p.Ser457Tyr	missense_variant	Exon 11 of 25	ENST00000407559.8	NP_060521.4	Q8WVS4A0A140VK66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DYNC2I1	ENST00000407559.8 link	c.1370C>A	p.Ser457Tyr	missense_variant	Exon 11 of 25	1	NM_018051.5	ENSP00000384290.3	Q8WVS4
DYNC2I1	ENST00000444851.5 link	n.701C>A		non_coding_transcript_exon_variant	Exon 7 of 20	1		ENSP00000392608.1	H7C022
DYNC2I1	ENST00000467220.1 link	n.3169C>A		non_coding_transcript_exon_variant	Exon 6 of 20	2

Frequencies

GnomAD3 genomes

AF:

0.00166

AC:

253

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00553

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000446

AC:

111

AN:

248852

Hom.:

AF XY:

0.000348

AC XY:

AN XY:

135026

show subpopulations

Gnomad AFR exome

AF:

0.00595

Gnomad AMR exome

AF:

0.000378

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000182

AC:

266

AN:

1461322

Hom.:

Cov.:

AF XY:

0.000182

AC XY:

132

AN XY:

726942

show subpopulations

Gnomad4 AFR exome

AF:

0.00600

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.00166

AC:

253

AN:

152276

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00551

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000208

Hom.:

Bravo

AF:

0.00198

ESP6500AA

AF:

0.00605

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000455

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DYNC2I1-related disorder

Benign:1

Apr 20, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Short-rib thoracic dysplasia 8 with or without polydactyly

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

0.10

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.067

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.57

M_CAP

Benign

0.014

MetaRNN

Benign

0.0068

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.9

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.13

Sift

Benign

0.19

Sift4G

Uncertain

0.013

Polyphen

1.0

Vest4

0.27

MVP

0.60

MPC

0.42

ClinPred

0.055

GERP RS

4.8

Varity_R

0.22

gMVP

0.21

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