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GeneBe

2-11193868-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

2
Splicing: ADA: 0.0006356
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.992
Variant links:
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]

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ACMG classification

Classification made for transcript

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
ROCK2NM_004850.5 linkuse as main transcriptc.3609-11A>C splice_polypyrimidine_tract_variant, intron_variant ENST00000315872.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ROCK2ENST00000315872.11 linkuse as main transcriptc.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
show subpopulations
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
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2271621; hg19: chr2-11333994; API