Genetic Variant CIT:p.Arg2009Cys (chr12-119690312-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_001206999.2(CIT):c.6025C>T(p.Arg2009Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000485 in 1,442,020 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

CIT
NM_001206999.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.22

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.6025C>T	p.Arg2009Cys	missense	Exon 47 of 48	NP_001193928.1	O14578-4
	CIT	NM_007174.3		c.5899C>T	p.Arg1967Cys	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.6025C>T	p.Arg2009Cys	missense	Exon 47 of 48	ENSP00000376306.2	O14578-4
CIT	ENST00000261833.11	TSL:1	c.5899C>T	p.Arg1967Cys	missense	Exon 46 of 47	ENSP00000261833.7	O14578-1
CIT	ENST00000928243.1		c.6022C>T	p.Arg2008Cys	missense	Exon 47 of 48	ENSP00000598302.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000443

AC:

AN:

225672

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000575

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000485

AC:

AN:

1442020

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

717930

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33004

American (AMR)

AF:

0.00

AC:

AN:

43110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25800

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39386

South Asian (SAS)

AF:

0.00

AC:

AN:

85400

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00000451

AC:

AN:

1109260

Other (OTH)

AF:

0.0000167

AC:

AN:

59952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.68

MetaSVM

Uncertain

0.024

MutationAssessor

Benign

0.97

PhyloP100

6.2

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.84

MutPred

0.25

Gain of ubiquitination at K1970 (P = 0.0212)

MVP

0.87

MPC

1.9

ClinPred

0.76

GERP RS

5.5

Varity_R

0.44

gMVP

0.40

Mutation Taster

=68/32

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

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