chr22-31253646-C-T

Variant names:

• chr22-31253646-C-T
• rs2267171
• NM_005569.4:c.117-4645C>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.117-4645C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0858 in 152,292 control chromosomes in the GnomAD database, including 857 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 0.086 (857 hom., cov: 33)
• Consequence: LIMK2 NM_005569.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIMK2	NM_005569.4	c.117-4645C>T		intron_variant	Intron 2 of 15	ENST00000331728.9	NP_005560.1
LIMK2	NM_001031801.2	c.54-4645C>T		intron_variant	Intron 1 of 14		NP_001026971.1
LIMK2	NM_016733.3	c.54-4645C>T		intron_variant	Intron 1 of 14		NP_057952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIMK2	ENST00000331728.9	c.117-4645C>T		intron_variant	Intron 2 of 15	1	NM_005569.4	ENSP00000332687.4

Frequencies

GnomAD3 genomes AF: 0.0857 AC: 13047 AN: 152174 Hom.: 855 Cov.: 33

Gnomad AFR AF: 0.0742

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0521

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.0829

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0685

Gnomad OTH AF: 0.0803

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

GnomAD4 genome AF: 0.0858 AC: 13061 AN: 152292 Hom.: 857 Cov.: 33 AF XY: 0.0882 AC XY: 6565 AN XY: 74474

African (AFR) AF: 0.0742 AC: 3083 AN: 41564

American (AMR) AF: 0.0572 AC: 875 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0521 AC: 181 AN: 3472

East Asian (EAS) AF: 0.402 AC: 2076 AN: 5166

South Asian (SAS) AF: 0.216 AC: 1043 AN: 4824

European-Finnish (FIN) AF: 0.0829 AC: 880 AN: 10616

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0685 AC: 4661 AN: 68022

Other (OTH) AF: 0.0842 AC: 178 AN: 2114

Alfa AF: 0.0770 Hom.: 117

Bravo AF: 0.0805

Asia WGS AF: 0.336 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.48
PhyloP100		0.036
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2267171; hg19: chr22-31649632;