NM_004850.5:c.462+3953T>C

Variant names:

• chr2-11245708-A-G
• rs6716817
• NM_004850.5:c.462+3953T>C

Variant summary

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

The NM_004850.5(ROCK2):​c.462+3953T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,958 control chromosomes in the GnomAD database, including 18,974 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 0.49 (18974 hom., cov: 32)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.563 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.462+3953T>C		intron	N/A	NP_004841.2
	ROCK2	NM_001321643.2		c.204+3953T>C		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.462+3953T>C		intron	N/A	ENSP00000317985.6	O75116
	ROCK2	ENST00000944889.1		c.462+3953T>C		intron	N/A	ENSP00000614948.1
	ROCK2	ENST00000697752.1		c.462+3953T>C		intron	N/A	ENSP00000513431.1	A0A8V8TL82

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74111 AN: 151840 Hom.: 18962 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.488 AC: 74152 AN: 151958 Hom.: 18974 Cov.: 32 AF XY: 0.485 AC XY: 35993 AN XY: 74252

African (AFR) AF: 0.349 AC: 14489 AN: 41478

American (AMR) AF: 0.573 AC: 8727 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1541 AN: 3472

East Asian (EAS) AF: 0.401 AC: 2073 AN: 5164

South Asian (SAS) AF: 0.508 AC: 2451 AN: 4822

European-Finnish (FIN) AF: 0.504 AC: 5307 AN: 10536

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37751 AN: 67928

Other (OTH) AF: 0.491 AC: 1035 AN: 2110

Alfa AF: 0.532 Hom.: 93615

Bravo AF: 0.485

Asia WGS AF: 0.444 AC: 1546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.9
DANN	Benign	0.67
PhyloP100		1.4
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: rs6716817; hg19: chr2-11385834;