rs12479227

Variant names:

• chr2-11254227-C-T
• rs12479227
• NM_004850.5:c.325-4429G>A

Variant summary

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

The NM_004850.5(ROCK2):​c.325-4429G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 152,184 control chromosomes in the GnomAD database, including 182 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 0.041 (182 hom., cov: 31)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 11 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROCK2	NM_004850.5	c.325-4429G>A		intron_variant	Intron 3 of 32	ENST00000315872.11	NP_004841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROCK2	ENST00000315872.11	c.325-4429G>A		intron_variant	Intron 3 of 32	1	NM_004850.5	ENSP00000317985.6

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6222 AN: 152066 Hom.: 182 Cov.: 31

Gnomad AFR AF: 0.00862

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0347

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0696

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0528

Gnomad OTH AF: 0.0464

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

GnomAD4 genome AF: 0.0408 AC: 6216 AN: 152184 Hom.: 182 Cov.: 31 AF XY: 0.0410 AC XY: 3047 AN XY: 74406

African (AFR) AF: 0.00860 AC: 357 AN: 41526

American (AMR) AF: 0.0346 AC: 529 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 239 AN: 3470

East Asian (EAS) AF: 0.130 AC: 673 AN: 5180

South Asian (SAS) AF: 0.0686 AC: 331 AN: 4824

European-Finnish (FIN) AF: 0.0335 AC: 355 AN: 10592

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0528 AC: 3592 AN: 67994

Other (OTH) AF: 0.0459 AC: 97 AN: 2112

Alfa AF: 0.0480 Hom.: 239

Bravo AF: 0.0405

Asia WGS AF: 0.0720 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.80
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: rs12479227; hg19: chr2-11394353;