chr2-11183150-T-A

Variant names:

• chr2-11183150-T-A
• rs978906
• NM_004850.5:c.*287A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004850.5(ROCK2):​c.*287A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,906 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ROCK2 NM_004850.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 27 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROCK2	NM_004850.5	c.*287A>T		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.*287A>T		3_prime_UTR_variant	Exon 33 of 33	1	NM_004850.5	ENSP00000317985.6

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151906 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 162000 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 83110

African (AFR) AF: 0.00 AC: 0 AN: 4664

American (AMR) AF: 0.00 AC: 0 AN: 4406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5880

East Asian (EAS) AF: 0.00 AC: 0 AN: 13154

South Asian (SAS) AF: 0.00 AC: 0 AN: 5336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 886

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 100200

Other (OTH) AF: 0.00 AC: 0 AN: 10340

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151906 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74162

African (AFR) AF: 0.00 AC: 0 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67926

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 50029

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.5
DANN	Benign	0.75
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs978906; hg19: chr2-11323276;