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GeneBe

2-11207815-T-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_004850.5(ROCK2):c.2460A>C(p.Leu820=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,612,994 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 14 hom., cov: 33)
Exomes 𝑓: 0.00069 ( 10 hom. )

Consequence

ROCK2
NM_004850.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.218
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 -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant 2-11207815-T-G is Benign according to our data. Variant chr2-11207815-T-G is described in ClinVar as [Benign]. Clinvar id is 3052771.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.218 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00698 (1063/152338) while in subpopulation AFR AF= 0.0243 (1011/41582). AF 95% confidence interval is 0.0231. There are 14 homozygotes in gnomad4. There are 521 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
High AC in GnomAd at 1067 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ROCK2NM_004850.5 linkuse as main transcriptc.2460A>C p.Leu820= synonymous_variant 20/33 ENST00000315872.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ROCK2ENST00000315872.11 linkuse as main transcriptc.2460A>C p.Leu820= synonymous_variant 20/331 NM_004850.5 P2

Frequencies

GnomAD3 genomes
AF:
0.00701
AC:
1067
AN:
152220
Hom.:
14
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0245
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00216
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00156
AC:
388
AN:
249176
Hom.:
3
AF XY:
0.00107
AC XY:
145
AN XY:
135192
show subpopulations
Gnomad AFR exome
AF:
0.0235
Gnomad AMR exome
AF:
0.000465
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000354
Gnomad OTH exome
AF:
0.000497
GnomAD4 exome
AF:
0.000691
AC:
1009
AN:
1460656
Hom.:
10
Cov.:
30
AF XY:
0.000572
AC XY:
416
AN XY:
726686
show subpopulations
Gnomad4 AFR exome
AF:
0.0251
Gnomad4 AMR exome
AF:
0.000761
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000423
Gnomad4 OTH exome
AF:
0.00136
GnomAD4 genome
AF:
0.00698
AC:
1063
AN:
152338
Hom.:
14
Cov.:
33
AF XY:
0.00699
AC XY:
521
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.0243
Gnomad4 AMR
AF:
0.00216
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00356
Hom.:
3
Bravo
AF:
0.00793
Asia WGS
AF:
0.000868
AC:
3
AN:
3472

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

ROCK2-related condition Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesAug 13, 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
-0.54
Cadd
Benign
3.9
Dann
Benign
0.65

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs55931955; hg19: chr2-11347941; API