rs2290156

chr2-11193082-G-Cchr2-11193082-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.3688-370C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,074 control chromosomes in the GnomAD database, including 5,390 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 0.25 (5390 hom., cov: 33)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROCK2	NM_004850.5	c.3688-370C>G		intron_variant		ENST00000315872.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROCK2	ENST00000315872.11	c.3688-370C>G		intron_variant		1	NM_004850.5	P2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37651 AN: 151956 Hom.: 5390 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.286

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.248 AC: 37663 AN: 152074 Hom.: 5390 Cov.: 33 AF XY: 0.254 AC XY: 18865 AN XY: 74300

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.289

Alfa AF: 0.254 Hom.: 787

Bravo AF: 0.239

Asia WGS AF: 0.433 AC: 1502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.7
Dann	Benign	0.39

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: rs2290156; hg19: chr2-11333208;