Genetic Variant DYNC2I1:p.Gln631Glu (chr7-158918839-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_018051.5(DYNC2I1):c.1891C>G(p.Gln631Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

DYNC2I1
NM_018051.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.37

Publications

1 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: Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine, 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35112506).

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.1891C>G	p.Gln631Glu	missense	Exon 15 of 25	NP_060521.4
DYNC2I1	NM_001350914.2		c.1753C>G	p.Gln585Glu	missense	Exon 15 of 25	NP_001337843.1
DYNC2I1	NM_001350915.2		c.1318C>G	p.Gln440Glu	missense	Exon 14 of 24	NP_001337844.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DYNC2I1	ENST00000407559.8	TSL:1 MANE Select	c.1891C>G	p.Gln631Glu	missense	Exon 15 of 25	ENSP00000384290.3	Q8WVS4
DYNC2I1	ENST00000444851.5	TSL:1	n.1222C>G		non_coding_transcript_exon	Exon 11 of 20	ENSP00000392608.1	H7C022
DYNC2I1	ENST00000860814.1		c.1966C>G	p.Gln656Glu	missense	Exon 16 of 26	ENSP00000530873.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.78

M_CAP

Benign

0.022

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.8

PhyloP100

6.4

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.9

REVEL

Benign

0.19

Sift

Benign

0.064

Sift4G

Benign

0.11

Polyphen

0.083

Vest4

0.51

MutPred

0.17

Loss of sheet (P = 0.0817)

MVP

0.71

MPC

0.14

ClinPred

0.91

GERP RS

4.2

Varity_R

0.19

gMVP

0.36

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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