rs2056103

Variant names:

• chr2-11224630-T-A
• rs2056103
• NM_004850.5:c.869-170A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-11224630-T-A
• chr2-11224630-T-C
• chr2-11224630-T-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.869-170A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,732 control chromosomes in the GnomAD database, including 17,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: 𝑓 0.46 (17474 hom., cov: 32)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.544 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.869-170A>T		intron	N/A	NP_004841.2
	ROCK2	NM_001321643.2		c.611-170A>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.869-170A>T		intron	N/A	ENSP00000317985.6	O75116
	ROCK2	ENST00000401753.5	TSL:1	c.140-170A>T		intron	N/A	ENSP00000385509.1	E9PF63
	ROCK2	ENST00000944889.1		c.869-170A>T		intron	N/A	ENSP00000614948.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69830 AN: 151628 Hom.: 17462 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.460 AC: 69861 AN: 151732 Hom.: 17474 Cov.: 32 AF XY: 0.461 AC XY: 34203 AN XY: 74146

African (AFR) AF: 0.259 AC: 10696 AN: 41354

American (AMR) AF: 0.550 AC: 8376 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1596 AN: 3470

East Asian (EAS) AF: 0.403 AC: 2078 AN: 5154

South Asian (SAS) AF: 0.508 AC: 2442 AN: 4806

European-Finnish (FIN) AF: 0.554 AC: 5815 AN: 10496

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.549 AC: 37279 AN: 67904

Other (OTH) AF: 0.461 AC: 971 AN: 2108

Alfa AF: 0.514 Hom.: 2664

Bravo AF: 0.446

Asia WGS AF: 0.434 AC: 1509 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.9
DANN	Benign	0.60
PhyloP100		0.34
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: rs2056103; hg19: chr2-11364756;