rs2122383

chr2-11296642-T-Achr2-11296642-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.142-8906A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,932 control chromosomes in the GnomAD database, including 13,419 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 0.39 (13419 hom., cov: 32)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROCK2	NM_004850.5	c.142-8906A>T		intron_variant		ENST00000315872.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROCK2	ENST00000315872.11	c.142-8906A>T		intron_variant		1	NM_004850.5	P2
ROCK2	ENST00000697752.1	c.142-8906A>T		intron_variant				A1
ROCK2	ENST00000261535.7	c.142-8906A>T		intron_variant, NMD_transcript_variant		5
ROCK2	ENST00000462366.1	n.164-8906A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59964 AN: 151814 Hom.: 13406 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.395 AC: 59997 AN: 151932 Hom.: 13419 Cov.: 32 AF XY: 0.395 AC XY: 29292 AN XY: 74240

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.418

Alfa AF: 0.294 Hom.: 793

Bravo AF: 0.393

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.89
Dann	Benign	0.40

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: rs2122383; hg19: chr2-11436768;