rs10178332

Variant names:

• chr2-11268891-C-A
• rs10178332
• NM_004850.5:c.324+17648G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-11268891-C-A
• chr2-11268891-C-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.324+17648G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 152,030 control chromosomes in the GnomAD database, including 51,155 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 0.81 (51155 hom., cov: 30)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.904
• Publications: 12 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 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.324+17648G>T		intron	N/A	NP_004841.2
	ROCK2	NM_001321643.2		c.66+17648G>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.324+17648G>T		intron	N/A	ENSP00000317985.6	O75116
	ROCK2	ENST00000944889.1		c.324+17648G>T		intron	N/A	ENSP00000614948.1
	ROCK2	ENST00000697752.1		c.324+17648G>T		intron	N/A	ENSP00000513431.1	A0A8V8TL82

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122639 AN: 151912 Hom.: 51133 Cov.: 30

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.954

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.837

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

GnomAD4 genome AF: 0.807 AC: 122709 AN: 152030 Hom.: 51155 Cov.: 30 AF XY: 0.813 AC XY: 60437 AN XY: 74318

African (AFR) AF: 0.576 AC: 23847 AN: 41408

American (AMR) AF: 0.864 AC: 13206 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 3207 AN: 3468

East Asian (EAS) AF: 0.995 AC: 5136 AN: 5164

South Asian (SAS) AF: 0.880 AC: 4237 AN: 4814

European-Finnish (FIN) AF: 0.954 AC: 10099 AN: 10582

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.885 AC: 60152 AN: 67996

Other (OTH) AF: 0.838 AC: 1767 AN: 2108

Alfa AF: 0.804 Hom.: 3030

Bravo AF: 0.791

Asia WGS AF: 0.914 AC: 3176 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.58
DANN	Benign	0.24
PhyloP100		-0.90
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: rs10178332; hg19: chr2-11409017;