Genetic Variant ROCK2:c.3609-11A>C (chr2-11193868-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004850.5(ROCK2):c.3609-11A>C variant causes a 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 intron

Scores

Splicing: ADA: 0.0006356

Clinical Significance

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

Conservation

PhyloP100: 0.992

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

congenital heart disease
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: ClinGen, PanelApp Australia

ROCK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004850.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK2	NM_004850.5	MANE Select	c.3609-11A>C		intron	N/A	NP_004841.2
	ROCK2	NM_001321643.2		c.3351-11A>C		intron	N/A	NP_001308572.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ROCK2	ENST00000315872.11	TSL:1 MANE Select	c.3609-11A>C	intron	N/A	ENSP00000317985.6	O75116
ROCK2	ENST00000401753.5	TSL:1	c.2880-11A>C	intron	N/A	ENSP00000385509.1	E9PF63
ROCK2	ENST00000944889.1		c.3786-11A>C	intron	N/A	ENSP00000614948.1

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

GnomAD2 exomes

AF:

0.301

AC:

70532

AN:

233996

AF XY:

0.306

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 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

African (AFR)

AF:

0.110

AC:

3478

AN:

31518

American (AMR)

AF:

0.262

AC:

11088

AN:

42292

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

7849

AN:

25292

East Asian (EAS)

AF:

0.524

AC:

20205

AN:

38550

South Asian (SAS)

AF:

0.331

AC:

27075

AN:

81892

European-Finnish (FIN)

AF:

0.329

AC:

16797

AN:

51116

Middle Eastern (MID)

AF:

0.311

AC:

1740

AN:

5602

European-Non Finnish (NFE)

AF:

0.277

AC:

290281

AN:

1049442

Other (OTH)

AF:

0.293

AC:

16858

AN:

57538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

11896

23793

35689

47586

59482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9618

19236

28854

38472

48090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.248

AC:

37656

AN:

152098

Hom.:

5391

Cov.:

AF XY:

0.254

AC XY:

18881

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.116

AC:

4804

AN:

41538

American (AMR)

AF:

0.251

AC:

3837

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

1123

AN:

3470

East Asian (EAS)

AF:

0.540

AC:

2797

AN:

5178

South Asian (SAS)

AF:

0.345

AC:

1664

AN:

4824

European-Finnish (FIN)

AF:

0.337

AC:

3562

AN:

10570

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.278

AC:

18878

AN:

67912

Other (OTH)

AF:

0.289

AC:

609

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1430

2859

4289

5718

7148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.273

Hom.:

2963

Bravo

AF:

0.239

Asia WGS

AF:

0.433

AC:

1496

AN:

3464

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

0.99

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over