rs17366517

Variant names:

• chr2-11180542-A-G
• rs17366517
• NM_004850.5:c.*2895T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.86).
• 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 rank	MANE	Protein	UniProt
ROCK2	NM_004850.5	c.*2895T>C		3_prime_UTR_variant	Exon 33 of 33	ENST00000315872.11	NP_004841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROCK2	ENST00000315872.11	c.*2895T>C		3_prime_UTR_variant	Exon 33 of 33	1	NM_004850.5	ENSP00000317985.6
ROCK2	ENST00000697752.1	c.*2895T>C		3_prime_UTR_variant	Exon 34 of 34			ENSP00000513431.1
ROCK2	ENST00000697790.1	c.*2912T>C		3_prime_UTR_variant	Exon 20 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0130 AC: 540 AN: 41570

American (AMR) AF: 0.0374 AC: 572 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4826

European-Finnish (FIN) AF: 0.0963 AC: 1021 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0664 AC: 4518 AN: 68018

Other (OTH) AF: 0.0430 AC: 91 AN: 2114

Alfa AF: 0.0559 Hom.: 357

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
PhyloP100		0.14
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: rs17366517; hg19: chr2-11320668;