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GeneBe

2-11201058-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP2PP3BP4

The NM_004850.5(ROCK2):c.2809T>C(p.Ser937Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ROCK2
NM_004850.5 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, ROCK2
PP3
Multiple lines of computational evidence support a deleterious effect 5: AlphaMissense, Cadd, FATHMM_MKL, phyloP100way_vertebrate, PrimateAI [when M_CAP, MetaRNN, MutationTaster was below the threshold]
BP4
Computational evidence support a benign effect (MetaRNN=0.33289415).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ROCK2NM_004850.5 linkuse as main transcriptc.2809T>C p.Ser937Pro missense_variant 23/33 ENST00000315872.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ROCK2ENST00000315872.11 linkuse as main transcriptc.2809T>C p.Ser937Pro missense_variant 23/331 NM_004850.5 P2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 GeneticsDec 15, 2022The c.2809T>C (p.S937P) alteration is located in exon 23 (coding exon 23) of the ROCK2 gene. This alteration results from a T to C substitution at nucleotide position 2809, causing the serine (S) at amino acid position 937 to be replaced by a proline (P). 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
Pathogenic
1.0
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
Cadd
Pathogenic
28
Dann
Uncertain
1.0
DEOGEN2
Benign
0.33
T;.;.
Eigen
Uncertain
0.67
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.33
T;T;T
MetaSVM
Benign
-0.51
T
MutationAssessor
Uncertain
2.3
M;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-2.5
N;.;N
REVEL
Uncertain
0.32
Sift
Benign
0.14
T;.;T
Sift4G
Benign
0.20
T;T;T
Polyphen
0.99
D;.;.
Vest4
0.47
MutPred
0.10
Loss of phosphorylation at S937 (P = 0.0165);.;.;
MVP
0.58
MPC
2.1
ClinPred
0.90
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.50
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-11341184; API