Genetic Variant NM_004850.5:c.1461+94C>T (chr2-11216064-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004850.5(ROCK2):c.1461+94C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 941,566 control chromosomes in the GnomAD database, including 102,373 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.38 ( 13019 hom., cov: 31)

Exomes 𝑓: 0.47 ( 89354 hom. )

Consequence

ROCK2
NM_004850.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.527

Publications

14 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.502 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.1461+94C>T		intron	N/A	NP_004841.2
	ROCK2	NM_001321643.2		c.1203+94C>T		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.1461+94C>T	intron	N/A	ENSP00000317985.6	O75116
ROCK2	ENST00000401753.5	TSL:1	c.732+94C>T	intron	N/A	ENSP00000385509.1	E9PF63
ROCK2	ENST00000944889.1		c.1461+94C>T	intron	N/A	ENSP00000614948.1

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

58197

AN:

151786

Hom.:

13008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.499

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.412

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.403

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.486

Gnomad OTH

AF:

0.412

GnomAD4 exome

AF:

0.470

AC:

371050

AN:

789662

Hom.:

89354

AF XY:

0.470

AC XY:

196618

AN XY:

418198

show subpopulations

African (AFR)

AF:

0.140

AC:

2747

AN:

19578

American (AMR)

AF:

0.556

AC:

21626

AN:

38910

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

8594

AN:

20758

East Asian (EAS)

AF:

0.408

AC:

14880

AN:

36452

South Asian (SAS)

AF:

0.450

AC:

30977

AN:

68800

European-Finnish (FIN)

AF:

0.413

AC:

21552

AN:

52156

Middle Eastern (MID)

AF:

0.451

AC:

1938

AN:

4296

European-Non Finnish (NFE)

AF:

0.492

AC:

251516

AN:

510864

Other (OTH)

AF:

0.455

AC:

17220

AN:

37848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

9311

18622

27934

37245

46556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4298

8596

12894

17192

21490

<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:

0.383

AC:

58226

AN:

151904

Hom.:

13019

Cov.:

AF XY:

0.382

AC XY:

28383

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.146

AC:

6041

AN:

41444

American (AMR)

AF:

0.511

AC:

7807

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.412

AC:

1429

AN:

3468

East Asian (EAS)

AF:

0.399

AC:

2058

AN:

5162

South Asian (SAS)

AF:

0.458

AC:

2204

AN:

4816

European-Finnish (FIN)

AF:

0.403

AC:

4227

AN:

10496

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.486

AC:

32996

AN:

67928

Other (OTH)

AF:

0.413

AC:

870

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1648

3296

4945

6593

8241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.462

Hom.:

21089

Bravo

AF:

0.380

Asia WGS

AF:

0.408

AC:

1419

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.6

(source)

DANN

Benign

0.59

PhyloP100

-0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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