Genetic Variant DYNC2I1:p.Arg149Gly (chr7-158871517-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018051.5(DYNC2I1):c.445C>G(p.Arg149Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R149C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

DYNC2I1
NM_018051.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.190

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

short-rib thoracic dysplasia 8 with or without polydactyly
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P
Jeune syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
short rib-polydactyly syndrome, Verma-Naumoff type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DYNC2I1 links:

ENSG00000296853 (HGNC:):

ENSG00000296853 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.102228194).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018051.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DYNC2I1	NM_018051.5	MANE Select	c.445C>G	p.Arg149Gly	missense	Exon 3 of 25	NP_060521.4
DYNC2I1	NM_001350914.2		c.307C>G	p.Arg103Gly	missense	Exon 3 of 25	NP_001337843.1
DYNC2I1	NM_001350915.2		c.-73C>G		5_prime_UTR	Exon 3 of 24	NP_001337844.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DYNC2I1	ENST00000407559.8	TSL:1 MANE Select	c.445C>G	p.Arg149Gly	missense	Exon 3 of 25	ENSP00000384290.3
ENSG00000296853	ENST00000743042.1		n.293-3441G>C		intron	N/A
DYNC2I1	ENST00000397143.3	TSL:3	c.*18C>G		downstream_gene	N/A	ENSP00000380330.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.5

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0047

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.43

M_CAP

Benign

0.010

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

0.19

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.051

Sift

Benign

0.27

Sift4G

Uncertain

0.047

Polyphen

0.25

Vest4

0.20

MutPred

0.32

Gain of loop (P = 0.0097)

MVP

0.36

MPC

0.31

ClinPred

0.24

GERP RS

1.3

Varity_R

0.13

gMVP

0.019

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over