Genetic Variant DYNC1I2:p.Arg13His (chr2-171690193-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001378.3(DYNC1I2):c.38G>A(p.Arg13His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DYNC1I2
NM_001378.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.68

Publications

0 publications found

Variant links:

Genes affected

DYNC1I2 (HGNC:2964): (dynein cytoplasmic 1 intermediate chain 2) This gene encodes a member of the dynein intermediate chain family. The encoded protein is a non-catalytic component of the cytoplasmic dynein 1 complex, which acts as a retrograde microtubule motor to transport organelles and vesicles. A pseudogene of this gene is located on chromosome 10. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

DYNC1I2 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with microcephaly and structural brain anomalies
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

DYNC1I2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC1I2	NM_001378.3 link	c.38G>A	p.Arg13His	missense_variant	Exon 2 of 18	ENST00000397119.8	NP_001369.1	Q13409-1A0A140VKE9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC1I2	ENST00000397119.8 link	c.38G>A	p.Arg13His	missense_variant	Exon 2 of 18	1	NM_001378.3	ENSP00000380308.3		Q13409-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1402862

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

692428

African (AFR)

AF:

0.00

AC:

AN:

31732

American (AMR)

AF:

0.00

AC:

AN:

36170

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25196

East Asian (EAS)

AF:

0.00

AC:

AN:

36310

South Asian (SAS)

AF:

0.00

AC:

AN:

78942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49840

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4896

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1081582

Other (OTH)

AF:

0.00

AC:

AN:

58194

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 03, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.38G>A (p.R13H) alteration is located in exon 2 (coding exon 1) of the DYNC1I2 gene. This alteration results from a G to A substitution at nucleotide position 38, causing the arginine (R) at amino acid position 13 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.34

T;.;D;.;T;.;.;T;.;D;.;.;T;T;T;.;.;.;T

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;.;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.68

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.53

MutationAssessor

Uncertain

2.9

.;M;M;M;.;M;M;.;M;M;.;M;.;.;.;.;.;.;.

PhyloP100

9.7

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-3.6

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

1.0

.;D;D;.;.;D;D;.;D;D;.;.;.;.;.;.;.;.;.

Vest4

0.48, 0.48, 0.53, 0.50, 0.49, 0.46, 0.47, 0.49

MutPred

0.23

Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);Loss of MoRF binding (P = 0.0203);

MVP

0.88

MPC

1.6

ClinPred

1.0

GERP RS

4.8

PromoterAI

-0.027

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.54

gMVP

0.19

Mutation Taster

=54/46

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over