Variant 2-11218994-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004850.5(ROCK2):c.1292C>A(p.Thr431Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 1,421,884 control chromosomes in the GnomAD database, including 179,796 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.46 ( 17221 hom., cov: 31)

Exomes 𝑓: 0.50 ( 162575 hom. )

Consequence

ROCK2
NM_004850.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.02

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:

ROCK2 (HGNC:):

ROCK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.8063906E-5).

BP6

Variant 2-11218994-G-T is Benign according to our data. Variant chr2-11218994-G-T is described in ClinVar as [Benign]. Clinvar id is 403387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROCK2	NM_004850.5 linkuse as main transcript	c.1292C>A	p.Thr431Asn	missense_variant	10/33	ENST00000315872.11	NP_004841.2	O75116A0A2P9DU05Q14DU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROCK2	ENST00000315872.11 linkuse as main transcript	c.1292C>A	p.Thr431Asn	missense_variant	10/33	1	NM_004850.5	ENSP00000317985.6		O75116

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69269

AN:

151766

Hom.:

17210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.510

Gnomad AMR

AF:

0.547

Gnomad ASJ

AF:

0.457

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.461

Gnomad FIN

AF:

0.545

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.546

Gnomad OTH

AF:

0.457

GnomAD3 exomes

AF:

0.486

AC:

104885

AN:

215796

Hom.:

26339

AF XY:

0.487

AC XY:

57789

AN XY:

118676

show subpopulations

Gnomad AFR exome

AF:

0.239

Gnomad AMR exome

AF:

0.538

Gnomad ASJ exome

AF:

0.441

Gnomad EAS exome

AF:

0.394

Gnomad SAS exome

AF:

0.435

Gnomad FIN exome

AF:

0.540

Gnomad NFE exome

AF:

0.527

Gnomad OTH exome

AF:

0.501

GnomAD4 exome

AF:

0.498

AC:

632733

AN:

1270000

Hom.:

162575

Cov.:

AF XY:

0.498

AC XY:

316639

AN XY:

635842

show subpopulations

Gnomad4 AFR exome

AF:

0.221

Gnomad4 AMR exome

AF:

0.541

Gnomad4 ASJ exome

AF:

0.440

Gnomad4 EAS exome

AF:

0.398

Gnomad4 SAS exome

AF:

0.427

Gnomad4 FIN exome

AF:

0.546

Gnomad4 NFE exome

AF:

0.515

Gnomad4 OTH exome

AF:

0.478

GnomAD4 genome

AF:

0.456

AC:

69300

AN:

151884

Hom.:

17221

Cov.:

AF XY:

0.456

AC XY:

33863

AN XY:

74210

show subpopulations

Gnomad4 AFR

AF:

0.257

Gnomad4 AMR

AF:

0.548

Gnomad4 ASJ

AF:

0.457

Gnomad4 EAS

AF:

0.402

Gnomad4 SAS

AF:

0.461

Gnomad4 FIN

AF:

0.545

Gnomad4 NFE

AF:

0.546

Gnomad4 OTH

AF:

0.458

Alfa

AF:

0.520

Hom.:

36008

Bravo

AF:

0.444

TwinsUK

AF:

0.537

AC:

1992

ALSPAC

AF:

0.517

AC:

1993

ESP6500AA

AF:

0.272

AC:

979

ESP6500EA

AF:

0.530

AC:

4295

ExAC

AF:

0.497

AC:

59968

Asia WGS

AF:

0.416

AC:

1450

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency, variant associated with chronic kidney disease -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.4

DANN

Benign

0.39

DEOGEN2

Benign

0.052

T;.

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.0094

LIST_S2

Benign

0.076

T;T

MetaRNN

Benign

0.000058

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.3

N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.30

N;N

REVEL

Benign

0.11

Sift

Benign

0.87

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.0

B;.

Vest4

0.029

MPC

0.90

ClinPred

0.0035

GERP RS

4.4

Varity_R

0.032

gMVP

0.11

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