chr7-150340602-C-A

Variant names:

• chr7-150340602-C-A
• rs990146697
• NM_002889.4:c.8G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RARRES2 NM_002889.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04370305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARRES2	NM_002889.4	c.8G>T	p.Arg3Leu	missense_variant	Exon 2 of 6	ENST00000223271.8	NP_002880.1
RARRES2	XR_007060121.1	n.80G>T		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.8G>T	p.Arg3Leu	missense_variant	Exon 2 of 6	1	NM_002889.4	ENSP00000223271.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1372054 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 673356

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.21
DANN	Benign	0.87
DEOGEN2	Benign	0.048	T;T;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.48	.;T;.;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.044	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;L;L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.089
Sift	Benign	0.66	T;T;T;T
Sift4G	Benign	0.61	T;.;T;T
Polyphen		0.0040	B;.;B;B
Vest4		0.12
MutPred		0.33		Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);
MVP		0.12
MPC		0.16
ClinPred		0.039	T
GERP RS		-9.4
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.058
gMVP		0.23

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

LitVar

Other links and lift over

dbSNP: rs990146697; hg19: chr7-150037691;