rs921322

Variant names:

• chr2-11179534-G-A
• rs921322
• NM_004850.5:c.*3903C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004850.5(ROCK2):​c.*3903C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,940 control chromosomes in the GnomAD database, including 13,412 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 0.40 (13412 hom., cov: 32)
• Consequence: ROCK2 NM_004850.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROCK2	NM_004850.5	c.*3903C>T		downstream_gene_variant		ENST00000315872.11	NP_004841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROCK2	ENST00000315872.11	c.*3903C>T		downstream_gene_variant		1	NM_004850.5	ENSP00000317985.6
ROCK2	ENST00000697752.1	c.*3903C>T		downstream_gene_variant				ENSP00000513431.1
ROCK2	ENST00000697790.1	c.*3920C>T		downstream_gene_variant				ENSP00000513442.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60061 AN: 151822 Hom.: 13398 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.396 AC: 60095 AN: 151940 Hom.: 13412 Cov.: 32 AF XY: 0.395 AC XY: 29313 AN XY: 74236

African (AFR) AF: 0.182 AC: 7557 AN: 41450

American (AMR) AF: 0.515 AC: 7859 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1432 AN: 3468

East Asian (EAS) AF: 0.401 AC: 2070 AN: 5162

South Asian (SAS) AF: 0.506 AC: 2436 AN: 4810

European-Finnish (FIN) AF: 0.402 AC: 4236 AN: 10536

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33034 AN: 67938

Other (OTH) AF: 0.416 AC: 876 AN: 2106

Alfa AF: 0.470 Hom.: 29256

Bravo AF: 0.392

Asia WGS AF: 0.424 AC: 1477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		-0.85

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs921322; hg19: chr2-11319660;