rs965665

chr2-11258749-C-G

Variant summary

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

The NM_004850.5(ROCK2):c.325-8951G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 150,788 control chromosomes in the GnomAD database, including 56,606 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 0.86 (56606 hom., cov: 30)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROCK2	NM_004850.5	c.325-8951G>C		intron_variant		ENST00000315872.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROCK2	ENST00000315872.11	c.325-8951G>C		intron_variant		1	NM_004850.5	P2

Frequencies

GnomAD3 genomes AF: 0.860 AC: 129527 AN: 150672 Hom.: 56554 Cov.: 30

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.954

Gnomad MID AF: 0.847

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.874

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

GnomAD4 genome AF: 0.860 AC: 129631 AN: 150788 Hom.: 56606 Cov.: 30 AF XY: 0.864 AC XY: 63673 AN XY: 73716

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.884

Gnomad4 ASJ AF: 0.933

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.882

Gnomad4 FIN AF: 0.954

Gnomad4 NFE AF: 0.886

Gnomad4 OTH AF: 0.875

Alfa AF: 0.873 Hom.: 7295

Bravo AF: 0.849

Asia WGS AF: 0.925 AC: 3212 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	4.6
Dann	Benign	0.49
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: rs965665; hg19: chr2-11398875;