Variant chr2-11193868-T-G 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.3609-11A>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,535,340 control chromosomes in the GnomAD database, including 64,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5391 hom., cov: 32)

Exomes 𝑓: 0.29 ( 59276 hom. )

Consequence

ROCK2
NM_004850.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0006356

Clinical Significance

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

Conservation

PhyloP100: 0.992

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 2-11193868-T-G is Benign according to our data. Variant chr2-11193868-T-G is described in ClinVar as [Benign]. Clinvar id is 403386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 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.3609-11A>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000315872.11	NP_004841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROCK2	ENST00000315872.11 linkuse as main transcript	c.3609-11A>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004850.5	ENSP00000317985	P2

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37644

AN:

151980

Hom.:

5391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.324

Gnomad EAS

AF:

0.540

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.286

GnomAD3 exomes

AF:

0.301

AC:

70532

AN:

233996

Hom.:

11516

AF XY:

0.306

AC XY:

39024

AN XY:

127416

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.265

Gnomad ASJ exome

AF:

0.309

Gnomad EAS exome

AF:

0.533

Gnomad SAS exome

AF:

0.338

Gnomad FIN exome

AF:

0.334

Gnomad NFE exome

AF:

0.285

Gnomad OTH exome

AF:

0.299

GnomAD4 exome

AF:

0.286

AC:

395371

AN:

1383242

Hom.:

59276

Cov.:

AF XY:

0.288

AC XY:

199106

AN XY:

691646

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.262

Gnomad4 ASJ exome

AF:

0.310

Gnomad4 EAS exome

AF:

0.524

Gnomad4 SAS exome

AF:

0.331

Gnomad4 FIN exome

AF:

0.329

Gnomad4 NFE exome

AF:

0.277

Gnomad4 OTH exome

AF:

0.293

GnomAD4 genome

AF:

0.248

AC:

37656

AN:

152098

Hom.:

5391

Cov.:

AF XY:

0.254

AC XY:

18881

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.251

Gnomad4 ASJ

AF:

0.324

Gnomad4 EAS

AF:

0.540

Gnomad4 SAS

AF:

0.345

Gnomad4 FIN

AF:

0.337

Gnomad4 NFE

AF:

0.278

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.270

Hom.:

1690

Bravo

AF:

0.239

Asia WGS

AF:

0.433

AC:

1496

AN:

3464

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 -

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

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00064

dbscSNV1_RF

Benign

0.056

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