rs12622447

Variant names:

• chr2-11335319-G-A
• rs12622447
• NM_004850.5:c.141+8677C>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.141+8677C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,046 control chromosomes in the GnomAD database, including 5,351 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 0.25 (5351 hom., cov: 32)
• Consequence: ROCK2 NM_004850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROCK2	NM_004850.5	c.141+8677C>T		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+8677C>T		intron_variant	Intron 1 of 32	1	NM_004850.5	ENSP00000317985.6
ROCK2	ENST00000697752.1	c.141+8677C>T		intron_variant	Intron 1 of 33			ENSP00000513431.1
ROCK2	ENST00000261535.7	n.141+8677C>T		intron_variant	Intron 1 of 14	5		ENSP00000261535.3
ROCK2	ENST00000462366.1	n.163+12849C>T		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37473 AN: 151928 Hom.: 5352 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.246 AC: 37475 AN: 152046 Hom.: 5351 Cov.: 32 AF XY: 0.253 AC XY: 18790 AN XY: 74316

African (AFR) AF: 0.113 AC: 4691 AN: 41504

American (AMR) AF: 0.248 AC: 3781 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1130 AN: 3472

East Asian (EAS) AF: 0.539 AC: 2790 AN: 5172

South Asian (SAS) AF: 0.345 AC: 1661 AN: 4818

European-Finnish (FIN) AF: 0.337 AC: 3557 AN: 10544

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18877 AN: 67978

Other (OTH) AF: 0.287 AC: 605 AN: 2106

Alfa AF: 0.271 Hom.: 2761

Bravo AF: 0.238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.51
PhyloP100		-0.35
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: rs12622447; hg19: chr2-11475445;