2-11248168-A-G

Variant names:

• chr2-11248168-A-G
• rs4477886
• NM_004850.5:c.462+1493T>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+1493T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 149,246 control chromosomes in the GnomAD database, including 18,663 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 (18663 hom., cov: 25)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROCK2	NM_004850.5	c.462+1493T>C		intron_variant	Intron 4 of 32	ENST00000315872.11	NP_004841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROCK2	ENST00000315872.11	c.462+1493T>C		intron_variant	Intron 4 of 32	1	NM_004850.5	ENSP00000317985.6

Frequencies

GnomAD3 genomes AF: 0.489 AC: 72970 AN: 149138 Hom.: 18650 Cov.: 25

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.489 AC: 73012 AN: 149246 Hom.: 18663 Cov.: 25 AF XY: 0.485 AC XY: 35307 AN XY: 72730

African (AFR) AF: 0.346 AC: 14068 AN: 40660

American (AMR) AF: 0.573 AC: 8592 AN: 15004

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1530 AN: 3440

East Asian (EAS) AF: 0.412 AC: 2018 AN: 4904

South Asian (SAS) AF: 0.516 AC: 2378 AN: 4610

European-Finnish (FIN) AF: 0.511 AC: 5066 AN: 9910

Middle Eastern (MID) AF: 0.493 AC: 143 AN: 290

European-Non Finnish (NFE) AF: 0.557 AC: 37563 AN: 67452

Other (OTH) AF: 0.493 AC: 1024 AN: 2078

Alfa AF: 0.496 Hom.: 5837

Bravo AF: 0.484

Asia WGS AF: 0.443 AC: 1542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.86
PhyloP100		-0.064
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: rs4477886; hg19: chr2-11388294;