22-31251108-A-G

Variant names:

• chr22-31251108-A-G
• rs4820043
• NM_005569.4:c.117-7183A>G

Variant summary

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

The NM_005569.4(LIMK2):​c.117-7183A>G 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 152,218 control chromosomes in the GnomAD database, including 48,475 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 (48475 hom., cov: 32)
• Consequence: LIMK2 NM_005569.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196
• Publications: 22 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIMK2	NM_005569.4	c.117-7183A>G		intron_variant	Intron 2 of 15	ENST00000331728.9	NP_005560.1
LIMK2	NM_001031801.2	c.53+2339A>G		intron_variant	Intron 1 of 14		NP_001026971.1
LIMK2	NM_016733.3	c.53+2339A>G		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.117-7183A>G		intron_variant	Intron 2 of 15	1	NM_005569.4	ENSP00000332687.4

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120140 AN: 152100 Hom.: 48422 Cov.: 32

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.762

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: 120248 AN: 152218 Hom.: 48475 Cov.: 32 AF XY: 0.787 AC XY: 58588 AN XY: 74402

African (AFR) AF: 0.947 AC: 39370 AN: 41554

American (AMR) AF: 0.761 AC: 11642 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 2802 AN: 3472

East Asian (EAS) AF: 0.877 AC: 4553 AN: 5190

South Asian (SAS) AF: 0.789 AC: 3804 AN: 4822

European-Finnish (FIN) AF: 0.656 AC: 6940 AN: 10574

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

European-Non Finnish (NFE) AF: 0.714 AC: 48528 AN: 67992

Other (OTH) AF: 0.808 AC: 1709 AN: 2114

Alfa AF: 0.741 Hom.: 16236

Bravo AF: 0.805

Asia WGS AF: 0.860 AC: 2991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.73
PhyloP100		-0.20
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: rs4820043; hg19: chr22-31647094;