2-11311858-C-T

Variant names:

• chr2-11311858-C-T
• rs10203916
• NM_004850.5:c.142-24122G>A

Variant summary

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

The NM_004850.5(ROCK2):​c.142-24122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 152,212 control chromosomes in the GnomAD database, including 48,828 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 0.79 (48828 hom., cov: 34)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

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=-1.0).
• 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 rank	MANE	Protein	UniProt
ROCK2	NM_004850.5	c.142-24122G>A		intron_variant	Intron 1 of 32	ENST00000315872.11	NP_004841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROCK2	ENST00000315872.11	c.142-24122G>A		intron_variant	Intron 1 of 32	1	NM_004850.5	ENSP00000317985.6
ROCK2	ENST00000697752.1	c.142-24122G>A		intron_variant	Intron 1 of 33			ENSP00000513431.1
ROCK2	ENST00000261535.7	n.142-24122G>A		intron_variant	Intron 1 of 14	5		ENSP00000261535.3
ROCK2	ENST00000462366.1	n.164-24122G>A		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119538 AN: 152094 Hom.: 48803 Cov.: 34

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.922

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.786 AC: 119605 AN: 152212 Hom.: 48828 Cov.: 34 AF XY: 0.790 AC XY: 58801 AN XY: 74436

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.853

Gnomad4 ASJ AF: 0.922

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.862

Gnomad4 FIN AF: 0.910

Gnomad4 NFE AF: 0.874

Gnomad4 OTH AF: 0.820

Alfa AF: 0.867 Hom.: 108505

Bravo AF: 0.771

Asia WGS AF: 0.889 AC: 3090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.3
DANN	Benign	0.38

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: rs10203916; hg19: chr2-11451984;