2-11194258-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_004850.5(ROCK2):ā€‹c.3606A>Cā€‹(p.Ile1202=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000371 in 1,325,790 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: š‘“ 0.00080 ( 2 hom., cov: 32)
Exomes š‘“: 0.00032 ( 7 hom. )

Consequence

ROCK2
NM_004850.5 splice_region, synonymous

Scores

2
Splicing: ADA: 0.09573
2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.681
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 -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 2-11194258-T-G is Benign according to our data. Variant chr2-11194258-T-G is described in ClinVar as [Benign]. Clinvar id is 3039060.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=0.681 with no splicing effect.
BS2
High AC in GnomAd4 at 121 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ROCK2NM_004850.5 linkuse as main transcriptc.3606A>C p.Ile1202= splice_region_variant, synonymous_variant 29/33 ENST00000315872.11 NP_004841.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ROCK2ENST00000315872.11 linkuse as main transcriptc.3606A>C p.Ile1202= splice_region_variant, synonymous_variant 29/331 NM_004850.5 ENSP00000317985 P2

Frequencies

GnomAD3 genomes
AF:
0.000802
AC:
122
AN:
152070
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0177
Gnomad SAS
AF:
0.00310
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.00120
AC:
242
AN:
201192
Hom.:
3
AF XY:
0.00116
AC XY:
128
AN XY:
110722
show subpopulations
Gnomad AFR exome
AF:
0.000235
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0167
Gnomad SAS exome
AF:
0.000271
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000438
GnomAD4 exome
AF:
0.000316
AC:
371
AN:
1173602
Hom.:
7
Cov.:
16
AF XY:
0.000334
AC XY:
196
AN XY:
587078
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00742
Gnomad4 SAS exome
AF:
0.000739
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000111
Gnomad4 OTH exome
AF:
0.00114
GnomAD4 genome
AF:
0.000795
AC:
121
AN:
152188
Hom.:
2
Cov.:
32
AF XY:
0.000941
AC XY:
70
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.000313
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0175
Gnomad4 SAS
AF:
0.00310
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.0000664
Hom.:
0
Bravo
AF:
0.000706
Asia WGS
AF:
0.00786
AC:
27
AN:
3448

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

ROCK2-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMar 07, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
CADD
Benign
14
DANN
Benign
0.88
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.096
dbscSNV1_RF
Benign
0.23
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: rs55839233; hg19: chr2-11334384; API