rs2788478

Positions:

Variant summary

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

The NM_018051.5(DYNC2I1):c.818A>G(p.Gln273Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,610,718 control chromosomes in the GnomAD database, including 136,177 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18990 hom., cov: 33)

Exomes 𝑓: 0.39 ( 117187 hom. )

Consequence

DYNC2I1
NM_018051.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.177

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:

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=2.2566614E-6).

BP6

Variant 7-158879928-A-G is Benign according to our data. Variant chr7-158879928-A-G is described in ClinVar as [Benign]. Clinvar id is 516219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC2I1	NM_018051.5 linkuse as main transcript	c.818A>G	p.Gln273Arg	missense_variant	5/25	ENST00000407559.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC2I1	ENST00000407559.8 linkuse as main transcript	c.818A>G	p.Gln273Arg	missense_variant	5/25	1	NM_018051.5	P1
DYNC2I1	ENST00000444851.5 linkuse as main transcript	c.149A>G	p.Gln50Arg	missense_variant, NMD_transcript_variant	1/20	1

Frequencies

GnomAD3 genomes

AF:

0.479

AC:

72760

AN:

151986

Hom.:

18949

Cov.:

show subpopulations

Gnomad AFR

AF:

0.679

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.458

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.722

Gnomad SAS

AF:

0.525

Gnomad FIN

AF:

0.374

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.365

Gnomad OTH

AF:

0.457

GnomAD3 exomes

AF:

0.439

AC:

107989

AN:

245938

Hom.:

25375

AF XY:

0.438

AC XY:

58580

AN XY:

133878

show subpopulations

Gnomad AFR exome

AF:

0.687

Gnomad AMR exome

AF:

0.427

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.713

Gnomad SAS exome

AF:

0.515

Gnomad FIN exome

AF:

0.377

Gnomad NFE exome

AF:

0.366

Gnomad OTH exome

AF:

0.411

GnomAD4 exome

AF:

0.392

AC:

571881

AN:

1458614

Hom.:

117187

Cov.:

AF XY:

0.395

AC XY:

286394

AN XY:

725872

show subpopulations

Gnomad4 AFR exome

AF:

0.689

Gnomad4 AMR exome

AF:

0.428

Gnomad4 ASJ exome

AF:

0.348

Gnomad4 EAS exome

AF:

0.700

Gnomad4 SAS exome

AF:

0.512

Gnomad4 FIN exome

AF:

0.378

Gnomad4 NFE exome

AF:

0.362

Gnomad4 OTH exome

AF:

0.412

GnomAD4 genome

AF:

0.479

AC:

72857

AN:

152104

Hom.:

18990

Cov.:

AF XY:

0.485

AC XY:

36049

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.679

Gnomad4 AMR

AF:

0.457

Gnomad4 ASJ

AF:

0.348

Gnomad4 EAS

AF:

0.722

Gnomad4 SAS

AF:

0.527

Gnomad4 FIN

AF:

0.374

Gnomad4 NFE

AF:

0.365

Gnomad4 OTH

AF:

0.456

Alfa

AF:

0.388

Hom.:

30464

Bravo

AF:

0.490

TwinsUK

AF:

0.373

AC:

1382

ALSPAC

AF:

0.363

AC:

1399

ESP6500AA

AF:

0.653

AC:

2463

ESP6500EA

AF:

0.367

AC:

3004

ExAC

AF:

0.441

AC:

53237

Asia WGS

AF:

0.605

AC:

2101

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Short-rib thoracic dysplasia 8 with or without polydactyly

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 13, 2017

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

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.18

DANN

Benign

0.12

DEOGEN2

Benign

0.00067

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00049

LIST_S2

Benign

0.13

MetaRNN

Benign

0.0000023

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

1.4

REVEL

Benign

0.013

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.014

MPC

0.085

ClinPred

0.00069

GERP RS

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.016

gMVP

0.034

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