rs726843

chr2-11216064-G-Achr2-11216064-G-Cchr2-11216064-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROCK2	NM_004850.5	c.1461+94C>T		intron_variant		ENST00000315872.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROCK2	ENST00000315872.11	c.1461+94C>T		intron_variant		1	NM_004850.5	P2

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58197 AN: 151786 Hom.: 13008 Cov.: 31

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

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.556

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.408

Gnomad4 SAS exome AF: 0.450

Gnomad4 FIN exome AF: 0.413

Gnomad4 NFE exome AF: 0.492

Gnomad4 OTH exome AF: 0.455

GnomAD4 genome AF: 0.383 AC: 58226 AN: 151904 Hom.: 13019 Cov.: 31 AF XY: 0.382 AC XY: 28383 AN XY: 74224

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.413

Alfa AF: 0.477 Hom.: 16574

Bravo AF: 0.380

Asia WGS AF: 0.408 AC: 1419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.6
Dann	Benign	0.59
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: rs726843; hg19: chr2-11356190; COSMIC: COSV55084436; COSMIC: COSV55084436;