chr2-11261412-T-C

Variant names:

• chr2-11261412-T-C
• rs4669700
• NM_004850.5:c.325-11614A>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.325-11614A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,192 control chromosomes in the GnomAD database, including 3,742 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 0.20 (3742 hom., cov: 33)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 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.325-11614A>G		intron	N/A	NP_004841.2
	ROCK2	NM_001321643.2		c.67-11614A>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.325-11614A>G		intron	N/A	ENSP00000317985.6	O75116
	ROCK2	ENST00000944889.1		c.325-11614A>G		intron	N/A	ENSP00000614948.1
	ROCK2	ENST00000697752.1		c.325-11614A>G		intron	N/A	ENSP00000513431.1	A0A8V8TL82

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30813 AN: 152074 Hom.: 3744 Cov.: 33

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.203 AC: 30822 AN: 152192 Hom.: 3742 Cov.: 33 AF XY: 0.209 AC XY: 15529 AN XY: 74402

African (AFR) AF: 0.106 AC: 4416 AN: 41532

American (AMR) AF: 0.214 AC: 3266 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1045 AN: 3472

East Asian (EAS) AF: 0.540 AC: 2799 AN: 5184

South Asian (SAS) AF: 0.339 AC: 1639 AN: 4828

European-Finnish (FIN) AF: 0.240 AC: 2544 AN: 10590

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14394 AN: 67990

Other (OTH) AF: 0.244 AC: 514 AN: 2108

Alfa AF: 0.213 Hom.: 6181

Bravo AF: 0.199

Asia WGS AF: 0.425 AC: 1475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
DANN	Benign	0.76
PhyloP100		0.074
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: rs4669700; hg19: chr2-11401538;