22-31249773-C-T

Variant names:

• chr22-31249773-C-T
• rs2106294
• NM_005569.4:c.117-8518C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005569.4(LIMK2):​c.117-8518C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,008 control chromosomes in the GnomAD database, including 48,413 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (48413 hom., cov: 30)
• Consequence: LIMK2 NM_005569.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.923
• Publications: 55 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

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.117-8518C>T		intron	N/A	NP_005560.1
	LIMK2	NM_001031801.2		c.53+1004C>T		intron	N/A	NP_001026971.1
	LIMK2	NM_016733.3		c.53+1004C>T		intron	N/A	NP_057952.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMK2	ENST00000331728.9	TSL:1 MANE Select	c.117-8518C>T		intron	N/A	ENSP00000332687.4
	LIMK2	ENST00000340552.4	TSL:1	c.53+1004C>T		intron	N/A	ENSP00000339916.4
	LIMK2	ENST00000333611.8	TSL:1	c.53+1004C>T		intron	N/A	ENSP00000330470.4

Frequencies

GnomAD3 genomes AF: 0.790 AC: 119987 AN: 151892 Hom.: 48361 Cov.: 30

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.790 AC: 120093 AN: 152008 Hom.: 48413 Cov.: 30 AF XY: 0.787 AC XY: 58489 AN XY: 74276

African (AFR) AF: 0.947 AC: 39317 AN: 41500

American (AMR) AF: 0.761 AC: 11628 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 2800 AN: 3470

East Asian (EAS) AF: 0.877 AC: 4522 AN: 5156

South Asian (SAS) AF: 0.789 AC: 3797 AN: 4814

European-Finnish (FIN) AF: 0.656 AC: 6924 AN: 10548

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48502 AN: 67930

Other (OTH) AF: 0.809 AC: 1702 AN: 2104

Alfa AF: 0.747 Hom.: 131287

Bravo AF: 0.805

Asia WGS AF: 0.860 AC: 2990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.2
DANN	Benign	0.85
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2106294; hg19: chr22-31645759;