2-11225874-T-A

Variant names:

• chr2-11225874-T-A
• rs10167277
• NM_004850.5:c.868+1380A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004850.5(ROCK2):​c.868+1380A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,028 control chromosomes in the GnomAD database, including 8,307 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 0.33 (8307 hom., cov: 32)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 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.868+1380A>T		intron	N/A	NP_004841.2
	ROCK2	NM_001321643.2		c.610+1380A>T		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.868+1380A>T		intron	N/A	ENSP00000317985.6	O75116
	ROCK2	ENST00000401753.5	TSL:1	c.139+1380A>T		intron	N/A	ENSP00000385509.1	E9PF63
	ROCK2	ENST00000944889.1		c.868+1380A>T		intron	N/A	ENSP00000614948.1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49399 AN: 151910 Hom.: 8303 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.325 AC: 49435 AN: 152028 Hom.: 8307 Cov.: 32 AF XY: 0.329 AC XY: 24421 AN XY: 74286

African (AFR) AF: 0.278 AC: 11541 AN: 41476

American (AMR) AF: 0.303 AC: 4639 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1604 AN: 3470

East Asian (EAS) AF: 0.548 AC: 2832 AN: 5164

South Asian (SAS) AF: 0.356 AC: 1718 AN: 4830

European-Finnish (FIN) AF: 0.361 AC: 3803 AN: 10530

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22096 AN: 67954

Other (OTH) AF: 0.360 AC: 761 AN: 2112

Alfa AF: 0.311 Hom.: 937

Bravo AF: 0.324

Asia WGS AF: 0.455 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.097
DANN	Benign	0.63
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10167277; hg19: chr2-11366000;