chr2-11296642-T-A

Variant names:

• chr2-11296642-T-A
• rs2122383
• NM_004850.5:c.142-8906A>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.142-8906A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,932 control chromosomes in the GnomAD database, including 13,419 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 0.39 (13419 hom., cov: 32)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.507 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK2	NM_004850.5	MANE Select	c.142-8906A>T		intron	N/A	NP_004841.2
	ROCK2	NM_001321643.2		c.-117-8906A>T		intron	N/A	NP_001308572.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK2	ENST00000315872.11	TSL:1 MANE Select	c.142-8906A>T		intron	N/A	ENSP00000317985.6
	ROCK2	ENST00000697752.1		c.142-8906A>T		intron	N/A	ENSP00000513431.1
	ROCK2	ENST00000261535.7	TSL:5	n.142-8906A>T		intron	N/A	ENSP00000261535.3

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59964 AN: 151814 Hom.: 13406 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.395 AC: 59997 AN: 151932 Hom.: 13419 Cov.: 32 AF XY: 0.395 AC XY: 29292 AN XY: 74240

African (AFR) AF: 0.177 AC: 7348 AN: 41458

American (AMR) AF: 0.517 AC: 7899 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1430 AN: 3466

East Asian (EAS) AF: 0.402 AC: 2076 AN: 5168

South Asian (SAS) AF: 0.504 AC: 2425 AN: 4814

European-Finnish (FIN) AF: 0.408 AC: 4294 AN: 10536

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33064 AN: 67906

Other (OTH) AF: 0.418 AC: 881 AN: 2106

Alfa AF: 0.294 Hom.: 793

Bravo AF: 0.393

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.89
DANN	Benign	0.40
PhyloP100		-0.17
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: rs2122383; hg19: chr2-11436768;