rs752852649

Variant names:

• chr2-11200982-G-A
• rs752852649
• NM_004850.5:c.2885C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-11200982-G-A
• chr2-11200982-G-C
• chr2-11200982-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004850.5(ROCK2):​c.2885C>T​(p.Thr962Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000079 in 1,594,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000083 (0 hom.)
• Consequence: ROCK2 NM_004850.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.044330597).
• BS2: High AC in GnomAd4 at 7 AD gene.

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.2885C>T	p.Thr962Met	missense	Exon 23 of 33	NP_004841.2
	ROCK2	NM_001321643.2		c.2627C>T	p.Thr876Met	missense	Exon 23 of 33	NP_001308572.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK2	ENST00000315872.11	TSL:1 MANE Select	c.2885C>T	p.Thr962Met	missense	Exon 23 of 33	ENSP00000317985.6	O75116
	ROCK2	ENST00000401753.5	TSL:1	c.2156C>T	p.Thr719Met	missense	Exon 19 of 29	ENSP00000385509.1	E9PF63
	ROCK2	ENST00000944889.1		c.2885C>T	p.Thr962Met	missense	Exon 23 of 34	ENSP00000614948.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152096 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000105 AC: 24 AN: 228426 AF XY: 0.000113

Gnomad AFR exome AF: 0.0000663

Gnomad AMR exome AF: 0.000208

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000748

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000825 AC: 119 AN: 1442396 Hom.: 0 Cov.: 31 AF XY: 0.0000907 AC XY: 65 AN XY: 716664

African (AFR) AF: 0.0000311 AC: 1 AN: 32190

American (AMR) AF: 0.000152 AC: 6 AN: 39598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25254

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39508

South Asian (SAS) AF: 0.000197 AC: 16 AN: 81120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53164

Middle Eastern (MID) AF: 0.000528 AC: 3 AN: 5682

European-Non Finnish (NFE) AF: 0.0000786 AC: 87 AN: 1106284

Other (OTH) AF: 0.0000671 AC: 4 AN: 59596

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152214 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74422

African (AFR) AF: 0.0000241 AC: 1 AN: 41528

American (AMR) AF: 0.000131 AC: 2 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000902 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.0000993 AC: 12

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.27	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.7
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.040
Sift	Benign	0.10	T
Sift4G	Benign	0.21	T
Polyphen		0.013	B
Vest4		0.18
MVP		0.31
MPC		0.96
ClinPred		0.021	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.039
gMVP		0.28
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs752852649; hg19: chr2-11341108; COSMIC: COSV59965940;