2-11257757-T-C

Position:

• chr2-11257757-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004850.5(ROCK2):​c.325-7959A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 151,024 control chromosomes in the GnomAD database, including 52,958 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 0.83 (52958 hom., cov: 31)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROCK2	NM_004850.5	c.325-7959A>G		intron_variant		ENST00000315872.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROCK2	ENST00000315872.11	c.325-7959A>G		intron_variant		1	NM_004850.5	P2

Frequencies

GnomAD3 genomes AF: 0.827 AC: 124811 AN: 150912 Hom.: 52908 Cov.: 31

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.930

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.848

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

GnomAD4 genome AF: 0.827 AC: 124910 AN: 151024 Hom.: 52958 Cov.: 31 AF XY: 0.829 AC XY: 61233 AN XY: 73856

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.930

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.863

Gnomad4 FIN AF: 0.910

Gnomad4 NFE AF: 0.875

Gnomad4 OTH AF: 0.850

Alfa AF: 0.823 Hom.: 2815

Bravo AF: 0.817

Asia WGS AF: 0.898 AC: 3120 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.9
DANN	Benign	0.47

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

Other links and lift over

dbSNP: rs1868584; hg19: chr2-11397883;