2-11180751-C-T

Variant names:

• chr2-11180751-C-T
• rs8996
• NM_004850.5:c.*2686G>A

Variant summary

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

The NM_004850.5(ROCK2):​c.*2686G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,940 control chromosomes in the GnomAD database, including 13,765 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 0.41 (13765 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ROCK2 NM_004850.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.853
• Publications: 11 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROCK2	NM_004850.5	c.*2686G>A		3_prime_UTR_variant	Exon 33 of 33	ENST00000315872.11	NP_004841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROCK2	ENST00000315872.11	c.*2686G>A		3_prime_UTR_variant	Exon 33 of 33	1	NM_004850.5	ENSP00000317985.6
ROCK2	ENST00000697752.1	c.*2686G>A		3_prime_UTR_variant	Exon 34 of 34			ENSP00000513431.1
ROCK2	ENST00000697790.1	c.*2703G>A		3_prime_UTR_variant	Exon 20 of 20			ENSP00000513442.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61658 AN: 151822 Hom.: 13753 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.423

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.406 AC: 61689 AN: 151940 Hom.: 13765 Cov.: 32 AF XY: 0.404 AC XY: 30031 AN XY: 74272

African (AFR) AF: 0.219 AC: 9082 AN: 41420

American (AMR) AF: 0.520 AC: 7935 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1433 AN: 3472

East Asian (EAS) AF: 0.400 AC: 2073 AN: 5182

South Asian (SAS) AF: 0.497 AC: 2395 AN: 4818

European-Finnish (FIN) AF: 0.402 AC: 4230 AN: 10532

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.487 AC: 33053 AN: 67934

Other (OTH) AF: 0.424 AC: 894 AN: 2110

Alfa AF: 0.475 Hom.: 19447

Bravo AF: 0.404

Asia WGS AF: 0.423 AC: 1470 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.7
DANN	Benign	0.83
PhyloP100		-0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs8996; hg19: chr2-11320877;