3-46408383-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003965.5(CCRL2):ā€‹c.304A>Gā€‹(p.Met102Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.000015 ( 0 hom. )

Consequence

CCRL2
NM_003965.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.211
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.24853289).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCRL2NM_003965.5 linkuse as main transcriptc.304A>G p.Met102Val missense_variant 2/2 ENST00000399036.4
CCRL2NM_001130910.2 linkuse as main transcriptc.340A>G p.Met114Val missense_variant 2/2
CCRL2XM_011534208.2 linkuse as main transcriptc.304A>G p.Met102Val missense_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCRL2ENST00000399036.4 linkuse as main transcriptc.304A>G p.Met102Val missense_variant 2/21 NM_003965.5 P2O00421-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000802
AC:
2
AN:
249468
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135336
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000150
AC:
22
AN:
1461878
Hom.:
0
Cov.:
34
AF XY:
0.00000825
AC XY:
6
AN XY:
727242
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:
0.0000198
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000827
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 24, 2023The c.340A>G (p.M114V) alteration is located in exon 2 (coding exon 2) of the CCRL2 gene. This alteration results from a A to G substitution at nucleotide position 340, causing the methionine (M) at amino acid position 114 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.064
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
0.015
DANN
Benign
0.55
DEOGEN2
Benign
0.18
T;.;T;T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.56
.;T;.;T;T
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.25
T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.5
L;.;L;.;L
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-2.3
N;N;N;N;N
REVEL
Benign
0.13
Sift
Benign
0.21
T;T;T;D;T
Sift4G
Benign
0.10
T;T;T;T;T
Polyphen
0.023
B;B;B;.;B
Vest4
0.088
MutPred
0.54
Gain of ubiquitination at K104 (P = 0.1111);.;Gain of ubiquitination at K104 (P = 0.1111);Gain of ubiquitination at K104 (P = 0.1111);Gain of ubiquitination at K104 (P = 0.1111);
MVP
0.15
MPC
0.030
ClinPred
0.075
T
GERP RS
-7.7
Varity_R
0.11
gMVP
0.30

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs764103950; hg19: chr3-46449874; API