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GeneBe

2-11192181-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate

The NM_004850.5(ROCK2):c.4130G>A(p.Arg1377Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000807 in 1,610,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ROCK2
NM_004850.5 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.96
Variant links:
Genes affected
ROCK2 (HGNC:10252): (Rho associated coiled-coil containing protein kinase 2) The protein encoded by this gene is a serine/threonine kinase that regulates cytokinesis, smooth muscle contraction, the formation of actin stress fibers and focal adhesions, and the activation of the c-fos serum response element. This protein, which is an isozyme of ROCK1 is a target for the small GTPase Rho. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP2
Missense variant where missense usually causes diseases, ROCK2
BP4
Computational evidence support a benign effect (MetaRNN=0.19174197).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ROCK2NM_004850.5 linkuse as main transcriptc.4130G>A p.Arg1377Gln missense_variant 32/33 ENST00000315872.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ROCK2ENST00000315872.11 linkuse as main transcriptc.4130G>A p.Arg1377Gln missense_variant 32/331 NM_004850.5 P2

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151536
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000121
AC:
3
AN:
248086
Hom.:
0
AF XY:
0.00000743
AC XY:
1
AN XY:
134562
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000754
AC:
11
AN:
1459192
Hom.:
0
Cov.:
32
AF XY:
0.00000689
AC XY:
5
AN XY:
725760
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000900
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151536
Hom.:
0
Cov.:
32
AF XY:
0.0000270
AC XY:
2
AN XY:
73956
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000675
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 28, 2023The c.4130G>A (p.R1377Q) alteration is located in exon 32 (coding exon 32) of the ROCK2 gene. This alteration results from a G to A substitution at nucleotide position 4130, causing the arginine (R) at amino acid position 1377 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.52
BayesDel_addAF
Uncertain
0.046
T
BayesDel_noAF
Benign
-0.11
Cadd
Pathogenic
26
Dann
Uncertain
1.0
DEOGEN2
Benign
0.067
T;.;.
Eigen
Benign
0.16
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Pathogenic
0.99
D;D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.19
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.0
N;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-0.13
N;.;N
REVEL
Benign
0.27
Sift
Benign
0.34
T;.;T
Sift4G
Benign
0.58
T;T;T
Polyphen
0.95
P;.;.
Vest4
0.43
MutPred
0.085
Loss of MoRF binding (P = 0.0861);.;.;
MVP
0.61
MPC
1.1
ClinPred
0.30
T
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.12
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1483703733; hg19: chr2-11332307; COSMIC: COSV59955850; COSMIC: COSV59955850; API