NM_002889.4:c.133T>C

Variant names:

• chr7-150340477-A-G
• rs186517902
• NM_002889.4:c.133T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002889.4(RARRES2):​c.133T>C​(p.Trp45Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RARRES2 NM_002889.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

Genes affected

RARRES2 (HGNC:9868): (retinoic acid receptor responder 2) This gene encodes a secreted chemotactic protein that initiates chemotaxis via the ChemR23 G protein-coupled seven-transmembrane domain ligand. Expression of this gene is upregulated by the synthetic retinoid tazarotene and occurs in a wide variety of tissues. The active protein has several roles, including that as an adipokine and as an antimicrobial protein with activity against bacteria and fungi. [provided by RefSeq, Nov 2014]

ENSG00000261305 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARRES2	NM_002889.4	c.133T>C	p.Trp45Arg	missense_variant	Exon 2 of 6	ENST00000223271.8	NP_002880.1
RARRES2	XR_007060121.1	n.205T>C		non_coding_transcript_exon_variant	Exon 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARRES2	ENST00000223271.8	c.133T>C	p.Trp45Arg	missense_variant	Exon 2 of 6	1	NM_002889.4	ENSP00000223271.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Benign	0.93
DEOGEN2	Benign	0.22	T;T;T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.60	.;T;.;T
M_CAP	Benign	0.0073	T
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M;.;M;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-6.1	D;D;D;D
REVEL	Benign	0.20
Sift	Benign	0.29	T;T;T;T
Sift4G	Uncertain	0.0050	D;.;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.65
MutPred		0.52		Gain of disorder (P = 0.0019);Gain of disorder (P = 0.0019);Gain of disorder (P = 0.0019);Gain of disorder (P = 0.0019);
MVP		0.17
MPC		0.37
ClinPred		0.76	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs186517902; hg19: chr7-150037566; COSMIC: COSV56231419; COSMIC: COSV56231419;