Variant 2-11208398-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_004850.5(ROCK2):c.2253G>C(p.Glu751Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000625 in 1,553,596 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 0.00052 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 0 hom. )

Consequence

ROCK2
NM_004850.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.360

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]

ROCK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP2

Missense variant where missense usually causes diseases, ROCK2

BP4

Computational evidence support a benign effect (MetaRNN=0.06375006).

BS2

High AC in GnomAd at 79 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROCK2	NM_004850.5 linkuse as main transcript	c.2253G>C	p.Glu751Asp	missense_variant	19/33	ENST00000315872.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROCK2	ENST00000315872.11 linkuse as main transcript	c.2253G>C	p.Glu751Asp	missense_variant	19/33	1	NM_004850.5	P2

Frequencies

GnomAD3 genomes

AF:

0.000520

AC:

AN:

151948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000285

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000912

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000592

AC:

141

AN:

238234

Hom.:

AF XY:

0.000578

AC XY:

AN XY:

129648

show subpopulations

Gnomad AFR exome

AF:

0.000273

Gnomad AMR exome

AF:

0.000686

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000691

Gnomad FIN exome

AF:

0.000329

Gnomad NFE exome

AF:

0.000929

Gnomad OTH exome

AF:

0.000876

GnomAD4 exome

AF:

0.000636

AC:

892

AN:

1401530

Hom.:

Cov.:

AF XY:

0.000657

AC XY:

457

AN XY:

695990

show subpopulations

Gnomad4 AFR exome

AF:

0.000308

Gnomad4 AMR exome

AF:

0.000770

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000527

Gnomad4 FIN exome

AF:

0.000496

Gnomad4 NFE exome

AF:

0.000726

Gnomad4 OTH exome

AF:

0.000700

GnomAD4 genome

AF:

0.000520

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000285

Gnomad4 NFE

AF:

0.000912

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000863

Hom.:

Bravo

AF:

0.000654

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000276

AC:

ESP6500EA

AF:

0.000980

AC:

ExAC

AF:

0.000662

AC:

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 submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.2253G>C (p.E751D) alteration is located in exon 19 (coding exon 19) of the ROCK2 gene. This alteration results from a G to C substitution at nucleotide position 2253, causing the glutamic acid (E) at amino acid position 751 to be replaced by an aspartic acid (D). 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

0.38

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.13

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.12

T;.;.

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.032

MetaRNN

Benign

0.064

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.5

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.98

N;.;N

REVEL

Benign

0.24

Sift

Benign

0.25

T;.;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.92

P;.;.

Vest4

0.55

MutPred

0.11

Loss of methylation at K749 (P = 0.0988);.;.;

MVP

0.77

MPC

0.47

ClinPred

0.064

GERP RS

0.056

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.26

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over