rs17366517

Positions:

• chr2-11180542-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004850.5(ROCK2):​c.*2895T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 152,298 control chromosomes in the GnomAD database, including 240 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 0.046 (240 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ROCK2 NM_004850.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROCK2	NM_004850.5	c.*2895T>C		3_prime_UTR_variant	33/33	ENST00000315872.11	NP_004841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROCK2	ENST00000315872	c.*2895T>C		3_prime_UTR_variant	33/33	1	NM_004850.5	ENSP00000317985.6
ROCK2	ENST00000697752	c.*2895T>C		3_prime_UTR_variant	34/34			ENSP00000513431.1
ROCK2	ENST00000697790	c.*2912T>C		3_prime_UTR_variant	20/20			ENSP00000513442.1

Frequencies

GnomAD3 genomes AF: 0.0462 AC: 7024 AN: 152180 Hom.: 239 Cov.: 32

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0374

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.0963

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0664

Gnomad OTH AF: 0.0435

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0461 AC: 7024 AN: 152298 Hom.: 240 Cov.: 32 AF XY: 0.0462 AC XY: 3443 AN XY: 74470

Gnomad4 AFR AF: 0.0130

Gnomad4 AMR AF: 0.0374

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.0963

Gnomad4 NFE AF: 0.0664

Gnomad4 OTH AF: 0.0430

Alfa AF: 0.0577 Hom.: 298

Bravo AF: 0.0408

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.6
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs17366517; hg19: chr2-11320668;