2-11271357-T-C

Variant names:

• chr2-11271357-T-C
• rs10929728
• NM_004850.5:c.324+15182A>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+15182A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,052 control chromosomes in the GnomAD database, including 8,224 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 0.32 (8224 hom., cov: 32)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.558
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK2	NM_004850.5	MANE Select	c.324+15182A>G		intron	N/A	NP_004841.2
	ROCK2	NM_001321643.2		c.66+15182A>G		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.324+15182A>G		intron	N/A	ENSP00000317985.6
	ROCK2	ENST00000697752.1		c.324+15182A>G		intron	N/A	ENSP00000513431.1
	ROCK2	ENST00000431087.2	TSL:3	c.183+15182A>G		intron	N/A	ENSP00000395957.2

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49124 AN: 151934 Hom.: 8220 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.323 AC: 49161 AN: 152052 Hom.: 8224 Cov.: 32 AF XY: 0.327 AC XY: 24267 AN XY: 74298

African (AFR) AF: 0.275 AC: 11399 AN: 41506

American (AMR) AF: 0.300 AC: 4589 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1599 AN: 3460

East Asian (EAS) AF: 0.540 AC: 2789 AN: 5168

South Asian (SAS) AF: 0.354 AC: 1699 AN: 4804

European-Finnish (FIN) AF: 0.358 AC: 3785 AN: 10568

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

European-Non Finnish (NFE) AF: 0.325 AC: 22098 AN: 67950

Other (OTH) AF: 0.361 AC: 760 AN: 2106

Alfa AF: 0.330 Hom.: 19908

Bravo AF: 0.322

Asia WGS AF: 0.451 AC: 1564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.0
DANN	Benign	0.86
PhyloP100		0.56
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: rs10929728; hg19: chr2-11411483;