2-11183150-T-C

Position:

• chr2-11183150-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROCK2	NM_004850.5	c.*287A>G		3_prime_UTR_variant	33/33	ENST00000315872.11	NP_004841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROCK2	ENST00000315872	c.*287A>G		3_prime_UTR_variant	33/33	1	NM_004850.5	ENSP00000317985.6

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

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.536

Gnomad4 ASJ exome AF: 0.421

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.515

Gnomad4 FIN exome AF: 0.419

Gnomad4 NFE exome AF: 0.495

Gnomad4 OTH exome AF: 0.459

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

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.425

Alfa AF: 0.475 Hom.: 32863

Bravo AF: 0.405

Asia WGS AF: 0.428 AC: 1489 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.4
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

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