Genetic Variant CIT:p.Val2053Leu (chr12-119690180-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_001206999.2(CIT):c.6157G>C(p.Val2053Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000075 in 1,334,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. V2053M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

CIT
NM_001206999.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.37

Publications

4 publications found

Variant links:

Genes affected

CIT (HGNC:1985): (citron rho-interacting serine/threonine kinase) This gene encodes a serine/threonine-protein kinase that functions in cell division. Together with the kinesin KIF14, this protein localizes to the central spindle and midbody, and functions to promote efficient cytokinesis. This protein is involved in central nervous system development. Polymorphisms in this gene are associated with bipolar disorder and risk for schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

CIT Gene-Disease associations (from GenCC):

microcephaly 17, primary, autosomal recessive
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
autosomal recessive primary microcephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CIT links:

Genome browser will be placed here

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=0.20060045).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206999.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIT	NM_001206999.2	MANE Select	c.6157G>C	p.Val2053Leu	missense	Exon 47 of 48	NP_001193928.1	O14578-4
	CIT	NM_007174.3		c.6031G>C	p.Val2011Leu	missense	Exon 46 of 47	NP_009105.1	O14578-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CIT	ENST00000392521.7	TSL:1 MANE Select	c.6157G>C	p.Val2053Leu	missense	Exon 47 of 48	ENSP00000376306.2	O14578-4
CIT	ENST00000261833.11	TSL:1	c.6031G>C	p.Val2011Leu	missense	Exon 46 of 47	ENSP00000261833.7	O14578-1
CIT	ENST00000928243.1		c.6154G>C	p.Val2052Leu	missense	Exon 47 of 48	ENSP00000598302.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000698

AC:

AN:

143286

AF XY:

0.0000127

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.50e-7

AC:

AN:

1334078

Hom.:

Cov.:

AF XY:

0.00000153

AC XY:

AN XY:

653306

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27910

American (AMR)

AF:

0.00

AC:

AN:

25908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19694

East Asian (EAS)

AF:

0.00

AC:

AN:

35480

South Asian (SAS)

AF:

0.0000155

AC:

AN:

64626

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5280

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1059242

Other (OTH)

AF:

0.00

AC:

AN:

55322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000842

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.015

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.66

MutationAssessor

Benign

0.69

PhyloP100

5.4

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.67

REVEL

Benign

0.091

Sift

Benign

0.034

Sift4G

Benign

0.061

Polyphen

0.15

Vest4

0.30

MutPred

0.20

Loss of relative solvent accessibility (P = 0.0404)

MVP

0.59

MPC

0.73

ClinPred

0.34

GERP RS

5.4

Varity_R

0.10

gMVP

0.098

Mutation Taster

=88/12

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over