rs6753921

Variant names:

• chr2-11186629-G-A
• rs6753921
• NM_004850.5:c.4164-3189C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-11186629-G-A
• chr2-11186629-G-C
• chr2-11186629-G-T

Variant summary

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

The NM_004850.5(ROCK2):​c.4164-3189C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,918 control chromosomes in the GnomAD database, including 13,723 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 0.41 (13723 hom., cov: 32)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481
• Publications: 7 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: LIMITED Submitted by: ClinGen

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 = 0.51 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.4164-3189C>T		intron	N/A	NP_004841.2
	ROCK2	NM_001321643.2		c.3906-3189C>T		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.4164-3189C>T		intron	N/A	ENSP00000317985.6	O75116
	ROCK2	ENST00000401753.5	TSL:1	c.3435-3189C>T		intron	N/A	ENSP00000385509.1	E9PF63
	ROCK2	ENST00000944889.1		c.4341-3189C>T		intron	N/A	ENSP00000614948.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61583 AN: 151800 Hom.: 13711 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.406 AC: 61614 AN: 151918 Hom.: 13723 Cov.: 32 AF XY: 0.404 AC XY: 29965 AN XY: 74214

African (AFR) AF: 0.219 AC: 9062 AN: 41436

American (AMR) AF: 0.519 AC: 7921 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1433 AN: 3472

East Asian (EAS) AF: 0.402 AC: 2073 AN: 5162

South Asian (SAS) AF: 0.498 AC: 2395 AN: 4812

European-Finnish (FIN) AF: 0.400 AC: 4203 AN: 10506

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33044 AN: 67960

Other (OTH) AF: 0.422 AC: 887 AN: 2104

Alfa AF: 0.464 Hom.: 8837

Bravo AF: 0.404

Asia WGS AF: 0.428 AC: 1489 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	0.34
DANN	Benign	0.45
PhyloP100		-0.48
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: rs6753921; hg19: chr2-11326755;