chr2-11190286-T-C

Variant names:

• chr2-11190286-T-C
• rs16857265
• NM_004850.5:c.4163+1862A>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.4163+1862A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0749 in 151,758 control chromosomes in the GnomAD database, including 625 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 0.075 (625 hom., cov: 31)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25
• Publications: 3 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=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 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.4163+1862A>G		intron	N/A	NP_004841.2
	ROCK2	NM_001321643.2		c.3905+1862A>G		intron	N/A	NP_001308572.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK2	ENST00000315872.11	TSL:1 MANE Select	c.4163+1862A>G		intron	N/A	ENSP00000317985.6	O75116
	ROCK2	ENST00000401753.5	TSL:1	c.3434+1862A>G		intron	N/A	ENSP00000385509.1	E9PF63
	ROCK2	ENST00000944889.1		c.4340+1862A>G		intron	N/A	ENSP00000614948.1

Frequencies

GnomAD3 genomes AF: 0.0748 AC: 11340 AN: 151642 Hom.: 625 Cov.: 31

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0521

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00998

Gnomad FIN AF: 0.0225

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.0734

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

GnomAD4 genome AF: 0.0749 AC: 11365 AN: 151758 Hom.: 625 Cov.: 31 AF XY: 0.0718 AC XY: 5327 AN XY: 74178

African (AFR) AF: 0.154 AC: 6375 AN: 41294

American (AMR) AF: 0.0520 AC: 794 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 481 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.0102 AC: 49 AN: 4806

European-Finnish (FIN) AF: 0.0225 AC: 236 AN: 10502

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0474 AC: 3218 AN: 67944

Other (OTH) AF: 0.0726 AC: 153 AN: 2106

Alfa AF: 0.0701 Hom.: 191

Bravo AF: 0.0823

Asia WGS AF: 0.0200 AC: 68 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		2.3
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: rs16857265; hg19: chr2-11330412;