2-11183150-T-C

Variant names:

• chr2-11183150-T-C
• rs978906
• NM_004850.5:c.*287A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004850.5(ROCK2):​c.*287A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 313,266 control chromosomes in the GnomAD database, including 32,202 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 0.41 (13753 hom., cov: 31)
  • Exomes 𝑓: 0.47 (18449 hom.)
• Consequence: ROCK2 NM_004850.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 27 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.51 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.*287A>G		3_prime_UTR	Exon 33 of 33	NP_004841.2
	ROCK2	NM_001321643.2		c.*287A>G		3_prime_UTR	Exon 33 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.*287A>G		3_prime_UTR	Exon 33 of 33	ENSP00000317985.6	O75116
	ROCK2	ENST00000944889.1		c.*287A>G		3_prime_UTR	Exon 34 of 34	ENSP00000614948.1
	ROCK2	ENST00000697752.1		c.*287A>G		3_prime_UTR	Exon 34 of 34	ENSP00000513431.1	A0A8V8TL82

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61655 AN: 151820 Hom.: 13741 Cov.: 31

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.468 AC: 75527 AN: 161326 Hom.: 18449 Cov.: 0 AF XY: 0.471 AC XY: 39009 AN XY: 82746

African (AFR) AF: 0.219 AC: 1018 AN: 4640

American (AMR) AF: 0.536 AC: 2354 AN: 4390

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 2467 AN: 5858

East Asian (EAS) AF: 0.400 AC: 5250 AN: 13110

South Asian (SAS) AF: 0.515 AC: 2739 AN: 5318

European-Finnish (FIN) AF: 0.419 AC: 7139 AN: 17056

Middle Eastern (MID) AF: 0.454 AC: 401 AN: 884

European-Non Finnish (NFE) AF: 0.495 AC: 49432 AN: 99772

Other (OTH) AF: 0.459 AC: 4727 AN: 10298

GnomAD4 genome AF: 0.406 AC: 61686 AN: 151940 Hom.: 13753 Cov.: 31 AF XY: 0.404 AC XY: 30008 AN XY: 74244

African (AFR) AF: 0.220 AC: 9136 AN: 41484

American (AMR) AF: 0.519 AC: 7924 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1431 AN: 3470

East Asian (EAS) AF: 0.402 AC: 2081 AN: 5174

South Asian (SAS) AF: 0.498 AC: 2395 AN: 4814

European-Finnish (FIN) AF: 0.401 AC: 4218 AN: 10530

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33010 AN: 67892

Other (OTH) AF: 0.425 AC: 897 AN: 2112

Alfa AF: 0.460 Hom.: 50029

Bravo AF: 0.405

Asia WGS AF: 0.428 AC: 1489 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.4
DANN	Benign	0.64
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs978906; hg19: chr2-11323276; COSMIC: COSV54468367; COSMIC: COSV54468367;