rs10178332

chr2-11268891-C-Achr2-11268891-C-G

Variant summary

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

The NM_004850.5(ROCK2):c.324+17648G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 152,030 control chromosomes in the GnomAD database, including 51,155 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 0.81 (51155 hom., cov: 30)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.904

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROCK2	NM_004850.5	c.324+17648G>T		intron_variant		ENST00000315872.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROCK2	ENST00000315872.11	c.324+17648G>T		intron_variant		1	NM_004850.5	P2

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122639 AN: 151912 Hom.: 51133 Cov.: 30

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.954

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.837

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

GnomAD4 genome AF: 0.807 AC: 122709 AN: 152030 Hom.: 51155 Cov.: 30 AF XY: 0.813 AC XY: 60437 AN XY: 74318

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.864

Gnomad4 ASJ AF: 0.925

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.880

Gnomad4 FIN AF: 0.954

Gnomad4 NFE AF: 0.885

Gnomad4 OTH AF: 0.838

Alfa AF: 0.826 Hom.: 2893

Bravo AF: 0.791

Asia WGS AF: 0.914 AC: 3176 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.58
Dann	Benign	0.24

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: rs10178332; hg19: chr2-11409017;