rs4141404

Positions:

• chr22-31279199-A-C
• chr22-31279199-A-G
• chr22-31279199-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005569.4(LIMK2):​c.*758A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,248 control chromosomes in the GnomAD database, including 48,685 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 (48673 hom., cov: 33)
  • Exomes 𝑓: 0.75 (12 hom.)
• Consequence: LIMK2 NM_005569.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.774

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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/exons	MANE	Protein	UniProt
LIMK2	NM_005569.4	c.*758A>C		3_prime_UTR_variant	16/16	ENST00000331728.9	NP_005560.1
LIMK2	NM_016733.3	c.*758A>C		3_prime_UTR_variant	15/15		NP_057952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIMK2	ENST00000331728.9	c.*758A>C		3_prime_UTR_variant	16/16	1	NM_005569.4	ENSP00000332687	A1
LIMK2	ENST00000333611.8	c.*758A>C		3_prime_UTR_variant	15/15	1		ENSP00000330470	P4

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120424 AN: 152090 Hom.: 48620 Cov.: 33

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.808

GnomAD4 exome AF: 0.750 AC: 30 AN: 40 Hom.: 12 Cov.: 0 AF XY: 0.846 AC XY: 22 AN XY: 26

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 0.700

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.792 AC: 120532 AN: 152208 Hom.: 48673 Cov.: 33 AF XY: 0.790 AC XY: 58784 AN XY: 74406

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.807

Gnomad4 EAS AF: 0.878

Gnomad4 SAS AF: 0.788

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.810

Alfa AF: 0.739 Hom.: 53578

Bravo AF: 0.806

Asia WGS AF: 0.861 AC: 2992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	15
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs4141404; hg19: chr22-31675185;