2-11193868-T-G

Variant names:

• chr2-11193868-T-G
• rs2271621
• NM_004850.5:c.3609-11A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004850.5(ROCK2):​c.3609-11A>C variant causes a 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 intron
• Scores: Splicing: ADA: 0.0006356
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.992
• Publications: 13 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 -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
ROCK2	NM_004850.5	c.3609-11A>C		intron_variant	Intron 29 of 32	ENST00000315872.11	NP_004841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROCK2	ENST00000315872.11	c.3609-11A>C		intron_variant	Intron 29 of 32	1	NM_004850.5	ENSP00000317985.6

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

GnomAD2 exomes AF: 0.301 AC: 70532 AN: 233996 AF XY: 0.306

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 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

African (AFR) AF: 0.110 AC: 3478 AN: 31518

American (AMR) AF: 0.262 AC: 11088 AN: 42292

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 7849 AN: 25292

East Asian (EAS) AF: 0.524 AC: 20205 AN: 38550

South Asian (SAS) AF: 0.331 AC: 27075 AN: 81892

European-Finnish (FIN) AF: 0.329 AC: 16797 AN: 51116

Middle Eastern (MID) AF: 0.311 AC: 1740 AN: 5602

European-Non Finnish (NFE) AF: 0.277 AC: 290281 AN: 1049442

Other (OTH) AF: 0.293 AC: 16858 AN: 57538

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

African (AFR) AF: 0.116 AC: 4804 AN: 41538

American (AMR) AF: 0.251 AC: 3837 AN: 15294

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

East Asian (EAS) AF: 0.540 AC: 2797 AN: 5178

South Asian (SAS) AF: 0.345 AC: 1664 AN: 4824

European-Finnish (FIN) AF: 0.337 AC: 3562 AN: 10570

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18878 AN: 67912

Other (OTH) AF: 0.289 AC: 609 AN: 2110

Alfa AF: 0.273 Hom.: 2963

Bravo AF: 0.239

Asia WGS AF: 0.433 AC: 1496 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.81
PhyloP100		0.99
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2271621; hg19: chr2-11333994; COSMIC: COSV107329264; COSMIC: COSV107329264;