18-20984522-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005406.3(ROCK1):c.2318C>G(p.Thr773Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,608,498 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0087 ( 11 hom., cov: 32)

Exomes 𝑓: 0.012 ( 123 hom. )

Consequence

ROCK1
NM_005406.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.46

Variant links:

Genes affected

ROCK1 (HGNC:10251): (Rho associated coiled-coil containing protein kinase 1) This gene encodes a protein serine/threonine kinase that is activated when bound to the GTP-bound form of Rho. The small GTPase Rho regulates formation of focal adhesions and stress fibers of fibroblasts, as well as adhesion and aggregation of platelets and lymphocytes by shuttling between the inactive GDP-bound form and the active GTP-bound form. Rho is also essential in cytokinesis and plays a role in transcriptional activation by serum response factor. This protein, a downstream effector of Rho, phosphorylates and activates LIM kinase, which in turn, phosphorylates cofilin, inhibiting its actin-depolymerizing activity. A pseudogene, related to this gene, is also located on chromosome 18. [provided by RefSeq, Aug 2015]

ROCK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042348504).

BP6

Variant 18-20984522-G-C is Benign according to our data. Variant chr18-20984522-G-C is described in ClinVar as [Benign]. Clinvar id is 777895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1331 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROCK1	NM_005406.3 link	c.2318C>G	p.Thr773Ser	missense_variant	Exon 20 of 33	ENST00000399799.3	NP_005397.1	Q13464

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROCK1	ENST00000399799.3 link	c.2318C>G	p.Thr773Ser	missense_variant	Exon 20 of 33	1	NM_005406.3	ENSP00000382697.1		Q13464
ROCK1	ENST00000635540.2 link	n.2318C>G		non_coding_transcript_exon_variant	Exon 20 of 34	5		ENSP00000489185.1		A0A0U1RQV4

Frequencies

GnomAD3 genomes

AF:

0.00876

AC:

1332

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00266

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00722

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.0147

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0136

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00932

AC:

2297

AN:

246472

Hom.:

AF XY:

0.00904

AC XY:

1205

AN XY:

133326

show subpopulations

Gnomad AFR exome

AF:

0.00205

Gnomad AMR exome

AF:

0.00266

Gnomad ASJ exome

AF:

0.00740

Gnomad EAS exome

AF:

0.0000553

Gnomad SAS exome

AF:

0.00408

Gnomad FIN exome

AF:

0.0181

Gnomad NFE exome

AF:

0.0136

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.0122

AC:

17761

AN:

1456312

Hom.:

123

Cov.:

AF XY:

0.0120

AC XY:

8713

AN XY:

724564

show subpopulations

Gnomad4 AFR exome

AF:

0.00145

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.00636

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00414

Gnomad4 FIN exome

AF:

0.0172

Gnomad4 NFE exome

AF:

0.0139

Gnomad4 OTH exome

AF:

0.0109

GnomAD4 genome

AF:

0.00875

AC:

1331

AN:

152186

Hom.:

Cov.:

AF XY:

0.00829

AC XY:

617

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.00722

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.0147

Gnomad4 NFE

AF:

0.0136

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00977

Hom.:

Bravo

AF:

0.00768

TwinsUK

AF:

0.0148

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.0130

AC:

112

ExAC

AF:

0.00942

AC:

1144

Asia WGS

AF:

0.00145

AC:

AN:

3470

EpiCase

AF:

0.0119

EpiControl

AF:

0.0117

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ROCK1: BP4, BS1, BS2 -

Jun 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.077

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.53

REVEL

Benign

0.11

Sift

Benign

0.42

Sift4G

Benign

0.75

Polyphen

0.0010

Vest4

0.068

MutPred

0.095

Gain of phosphorylation at T773 (P = 0.0751);

MVP

0.31

MPC

0.41

ClinPred

0.0099

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.074

gMVP

0.046

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