2-11193868-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004850.5(ROCK2):c.3609-11A>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,535,340 control chromosomes in the GnomAD database, including 64,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5391 hom., cov: 32)
  • Exomes 𝑓: 0.29 (59276 hom.)
• Consequence: ROCK2 NM_004850.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0006356
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.992

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 2-11193868-T-G is Benign according to our data. Variant chr2-11193868-T-G is described in ClinVar as [Benign]. Clinvar id is 403386.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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/exons	MANE	UniProt
ROCK2	NM_004850.5	c.3609-11A>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000315872.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROCK2	ENST00000315872.11	c.3609-11A>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004850.5	P2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37644 AN: 151980 Hom.: 5391 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.286

GnomAD3 exomes AF: 0.301 AC: 70532 AN: 233996 Hom.: 11516 AF XY: 0.306 AC XY: 39024 AN XY: 127416

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.265

Gnomad ASJ exome AF: 0.309

Gnomad EAS exome AF: 0.533

Gnomad SAS exome AF: 0.338

Gnomad FIN exome AF: 0.334

Gnomad NFE exome AF: 0.285

Gnomad OTH exome AF: 0.299

GnomAD4 exome AF: 0.286 AC: 395371 AN: 1383242 Hom.: 59276 Cov.: 21 AF XY: 0.288 AC XY: 199106 AN XY: 691646

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.262

Gnomad4 ASJ exome AF: 0.310

Gnomad4 EAS exome AF: 0.524

Gnomad4 SAS exome AF: 0.331

Gnomad4 FIN exome AF: 0.329

Gnomad4 NFE exome AF: 0.277

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.248 AC: 37656 AN: 152098 Hom.: 5391 Cov.: 32 AF XY: 0.254 AC XY: 18881 AN XY: 74340

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.289

Alfa AF: 0.270 Hom.: 1690

Bravo AF: 0.239

Asia WGS AF: 0.433 AC: 1496 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00064
dbscSNV1_RF	Benign	0.056
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: rs2271621; hg19: chr2-11333994;