2-11263326-C-T

Variant names:

• chr2-11263326-C-T
• rs4669702
• NM_004850.5:c.325-13528G>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.325-13528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,046 control chromosomes in the GnomAD database, including 5,352 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 0.25 (5352 hom., cov: 31)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROCK2	NM_004850.5	c.325-13528G>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.325-13528G>A		intron_variant	Intron 3 of 32	1	NM_004850.5	ENSP00000317985.6

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37551 AN: 151928 Hom.: 5353 Cov.: 31

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.247 AC: 37556 AN: 152046 Hom.: 5352 Cov.: 31 AF XY: 0.253 AC XY: 18819 AN XY: 74318

African (AFR) AF: 0.115 AC: 4792 AN: 41506

American (AMR) AF: 0.248 AC: 3791 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1123 AN: 3470

East Asian (EAS) AF: 0.540 AC: 2788 AN: 5166

South Asian (SAS) AF: 0.346 AC: 1667 AN: 4812

European-Finnish (FIN) AF: 0.336 AC: 3548 AN: 10556

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.278 AC: 18861 AN: 67958

Other (OTH) AF: 0.287 AC: 604 AN: 2108

Alfa AF: 0.125 Hom.: 236

Bravo AF: 0.239

Asia WGS AF: 0.432 AC: 1501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.2
DANN	Benign	0.58
PhyloP100		-0.27
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: rs4669702; hg19: chr2-11403452;