2-11320159-T-C

Variant names:

• chr2-11320159-T-C
• rs6755337
• NM_004850.5:c.141+23837A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004850.5(ROCK2):​c.141+23837A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,116 control chromosomes in the GnomAD database, including 42,487 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.73 (42487 hom., cov: 32)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 5 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]

ROCK2 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: ClinGen, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004850.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK2	NM_004850.5	MANE Select	c.141+23837A>G		intron	N/A	NP_004841.2
	ROCK2	NM_001321643.2		c.-118+25115A>G		intron	N/A	NP_001308572.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROCK2	ENST00000315872.11	TSL:1 MANE Select	c.141+23837A>G		intron	N/A	ENSP00000317985.6	O75116
	ROCK2	ENST00000944889.1		c.141+23837A>G		intron	N/A	ENSP00000614948.1
	ROCK2	ENST00000697752.1		c.141+23837A>G		intron	N/A	ENSP00000513431.1	A0A8V8TL82

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111044 AN: 151998 Hom.: 42461 Cov.: 32

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.783

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.730 AC: 111116 AN: 152116 Hom.: 42487 Cov.: 32 AF XY: 0.733 AC XY: 54472 AN XY: 74360

African (AFR) AF: 0.490 AC: 20305 AN: 41460

American (AMR) AF: 0.824 AC: 12595 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3036 AN: 3466

East Asian (EAS) AF: 0.942 AC: 4874 AN: 5176

South Asian (SAS) AF: 0.857 AC: 4140 AN: 4828

European-Finnish (FIN) AF: 0.767 AC: 8114 AN: 10578

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55351 AN: 68006

Other (OTH) AF: 0.786 AC: 1660 AN: 2112

Alfa AF: 0.792 Hom.: 24125

Bravo AF: 0.727

Asia WGS AF: 0.882 AC: 3066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.72
DANN	Benign	0.70
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6755337; hg19: chr2-11460285;