22-31267789-GC-AT

Variant names:

• chr22-31267789-GC-AT
• NM_005569.4:c.1142_1143delGCinsAT
• LIMK2 p.Arg381His

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_005569.4(LIMK2):​c.1142_1143delGCinsAT​(p.Arg381His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIMK2 NM_005569.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60
• Publications: 0 publications found

Genes affected

LIMK2 (HGNC:6614): (LIM domain kinase 2) There are approximately 40 known eukaryotic LIM proteins, so named for the LIM domains they contain. LIM domains are highly conserved cysteine-rich structures containing 2 zinc fingers. Although zinc fingers usually function by binding to DNA or RNA, the LIM motif probably mediates protein-protein interactions. LIM kinase-1 and LIM kinase-2 belong to a small subfamily with a unique combination of 2 N-terminal LIM motifs and a C-terminal protein kinase domain. The protein encoded by this gene is phosphorylated and activated by ROCK, a downstream effector of Rho, and the encoded protein, in turn, phosphorylates cofilin, inhibiting its actin-depolymerizing activity. It is thought that this pathway contributes to Rho-induced reorganization of the actin cytoskeleton. At least three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005569.4. 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
	LIMK2	NM_005569.4	MANE Select	c.1142_1143delGCinsAT	p.Arg381His	missense	N/A	NP_005560.1	P53671-1
	LIMK2	NM_001031801.2		c.1079_1080delGCinsAT	p.Arg360His	missense	N/A	NP_001026971.1	P53671-3
	LIMK2	NM_016733.3		c.1079_1080delGCinsAT	p.Arg360His	missense	N/A	NP_057952.1	P53671-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMK2	ENST00000331728.9	TSL:1 MANE Select	c.1142_1143delGCinsAT	p.Arg381His	missense	N/A	ENSP00000332687.4	P53671-1
	LIMK2	ENST00000340552.4	TSL:1	c.1079_1080delGCinsAT	p.Arg360His	missense	N/A	ENSP00000339916.4	P53671-3
	LIMK2	ENST00000333611.8	TSL:1	c.1079_1080delGCinsAT	p.Arg360His	missense	N/A	ENSP00000330470.4	P53671-2

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.6

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-31663775;