rs56127823

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003965.5(CCRL2):​c.659A>C​(p.Tyr220Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 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. Y220C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

CCRL2
NM_003965.5 missense

Scores

3
1
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.987
Variant links:
Genes affected
CCRL2 (HGNC:1612): (C-C motif chemokine receptor like 2) This gene encodes a chemokine receptor like protein, which is predicted to be a seven transmembrane protein and most closely related to CCR1. Chemokines and their receptors mediated signal transduction are critical for the recruitment of effector immune cells to the site of inflammation. This gene is expressed at high levels in primary neutrophils and primary monocytes, and is further upregulated on neutrophil activation and during monocyte to macrophage differentiation. The function of this gene is unknown. This gene is mapped to the region where the chemokine receptor gene cluster is located. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.848

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCRL2NM_003965.5 linkc.659A>C p.Tyr220Ser missense_variant Exon 2 of 2 ENST00000399036.4 NP_003956.2 O00421-1B2R8C0
CCRL2NM_001130910.2 linkc.695A>C p.Tyr232Ser missense_variant Exon 2 of 2 NP_001124382.1 O00421-2
CCRL2XM_011534208.2 linkc.659A>C p.Tyr220Ser missense_variant Exon 3 of 3 XP_011532510.1 O00421-1B2R8C0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCRL2ENST00000399036.4 linkc.659A>C p.Tyr220Ser missense_variant Exon 2 of 2 1 NM_003965.5 ENSP00000381994.3 O00421-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461780
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
727212
show subpopulations
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.058
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
5.8
DANN
Benign
0.76
DEOGEN2
Benign
0.32
T;.;T;T
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.85
FATHMM_MKL
Benign
0.38
N
LIST_S2
Benign
0.65
.;T;.;T
M_CAP
Benign
0.022
T
MetaRNN
Pathogenic
0.85
D;D;D;D
MetaSVM
Benign
-0.97
T
MutationAssessor
Pathogenic
3.3
M;.;M;M
PrimateAI
Benign
0.24
T
PROVEAN
Pathogenic
-6.8
D;D;D;D
REVEL
Benign
0.22
Sift
Benign
0.060
T;T;T;T
Sift4G
Uncertain
0.034
D;D;D;D
Polyphen
0.69
P;P;P;P
Vest4
0.24
MutPred
0.83
Loss of ubiquitination at K225 (P = 0.0839);.;Loss of ubiquitination at K225 (P = 0.0839);Loss of ubiquitination at K225 (P = 0.0839);
MVP
0.70
MPC
0.051
ClinPred
0.64
D
GERP RS
-8.3
Varity_R
0.22
gMVP
0.76

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-46450229; API