Genetic Variant NM_002889.4:c.8G>T (chr7-150340602-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002889.4(RARRES2):c.8G>T(p.Arg3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RARRES2
NM_002889.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.90

Publications

0 publications found

Variant links:

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]

RARRES2 links:

ENSG00000301866 (HGNC:):

ENSG00000301866 links:

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ACMG classification

Classification was made for transcript

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 (MetaRNN=0.04370305).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002889.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARRES2	NM_002889.4	MANE Select	c.8G>T	p.Arg3Leu	missense	Exon 2 of 6	NP_002880.1	A0A090N7U9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RARRES2	ENST00000223271.8	TSL:1 MANE Select	c.8G>T	p.Arg3Leu	missense	Exon 2 of 6	ENSP00000223271.3	Q99969
RARRES2	ENST00000482669.1	TSL:1	c.8G>T	p.Arg3Leu	missense	Exon 2 of 5	ENSP00000418483.1	Q99969
RARRES2	ENST00000466675.5	TSL:2	c.8G>T	p.Arg3Leu	missense	Exon 1 of 5	ENSP00000418009.1	Q99969

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1372054

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

673356

African (AFR)

AF:

0.00

AC:

AN:

31252

American (AMR)

AF:

0.00

AC:

AN:

34606

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24138

East Asian (EAS)

AF:

0.00

AC:

AN:

35822

South Asian (SAS)

AF:

0.00

AC:

AN:

78296

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5156

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1064682

Other (OTH)

AF:

0.00

AC:

AN:

56742

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.21

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.048

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.48

M_CAP

Benign

0.0017

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

-2.9

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.0

REVEL

Benign

0.089

Sift

Benign

0.66

Sift4G

Benign

0.61

Polyphen

0.0040

Vest4

0.12

MutPred

0.33

Loss of MoRF binding (P = 5e-04)

MVP

0.12

MPC

0.16

ClinPred

0.039

GERP RS

-9.4

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.058

gMVP

0.23

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over