2-11343366-A-G

Variant names:

• chr2-11343366-A-G
• rs10929732
• NM_004850.5:c.141+630T>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.141+630T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 152,114 control chromosomes in the GnomAD database, including 42,364 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 0.73 (42364 hom., cov: 32)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 6 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=-0.64).
• 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.141+630T>C		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.141+630T>C		intron_variant	Intron 1 of 32	1	NM_004850.5	ENSP00000317985.6
ROCK2	ENST00000697752.1	c.141+630T>C		intron_variant	Intron 1 of 33			ENSP00000513431.1
ROCK2	ENST00000261535.7	n.141+630T>C		intron_variant	Intron 1 of 14	5		ENSP00000261535.3
ROCK2	ENST00000462366.1	n.163+4802T>C		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110780 AN: 151996 Hom.: 42340 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.729 AC: 110850 AN: 152114 Hom.: 42364 Cov.: 32 AF XY: 0.731 AC XY: 54351 AN XY: 74368

African (AFR) AF: 0.484 AC: 20052 AN: 41454

American (AMR) AF: 0.824 AC: 12592 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3041 AN: 3472

East Asian (EAS) AF: 0.942 AC: 4883 AN: 5184

South Asian (SAS) AF: 0.858 AC: 4139 AN: 4822

European-Finnish (FIN) AF: 0.767 AC: 8103 AN: 10568

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55337 AN: 68008

Other (OTH) AF: 0.783 AC: 1654 AN: 2112

Alfa AF: 0.734 Hom.: 5505

Bravo AF: 0.725

Asia WGS AF: 0.883 AC: 3068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.3
DANN	Benign	0.79
PhyloP100		-0.043
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: rs10929732; hg19: chr2-11483492;