rs879253817

Positions:

• chr12-119876130-ATCCAAAGGAT-A

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_001206999.2(CIT):​c.29_38delATCCTTTGGA​(p.Asn10fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CIT NM_001206999.2 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:3
• Conservation: PhyloP100: 5.06

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.995 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 12-119876130-ATCCAAAGGAT-A is Pathogenic according to our data. Variant chr12-119876130-ATCCAAAGGAT-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 221283.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIT	NM_001206999.2	c.29_38delATCCTTTGGA	p.Asn10fs	frameshift_variant	2/48	ENST00000392521.7	NP_001193928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIT	ENST00000392521.7	c.29_38delATCCTTTGGA	p.Asn10fs	frameshift_variant	2/48	1	NM_001206999.2	ENSP00000376306.2
CIT	ENST00000261833.11	c.29_38delATCCTTTGGA	p.Asn10fs	frameshift_variant	2/47	1		ENSP00000261833.7

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, single submitter

Submissions by phenotype

Microcephaly 17, primary, autosomal recessive Pathogenic:2

Likely pathogenic, criteria provided, single submitter	research	Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	Oct 04, 2024	PVS1,PM2 -
Pathogenic, no assertion criteria provided	literature only	OMIM	Sep 02, 2016	- -

Autosomal recessive primary microcephaly Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Sbielas Lab-Department of Human Genetics University of Michigan, University of Michigan Medical School

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs879253817; hg19: chr12-120313934;