rs587777046

Variant summary

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

The NM_138409.4(MRAP2):​c.70G>A​(p.Glu24Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,150 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MRAP2
NM_138409.4 missense

Scores

1
11
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.31
Variant links:
Genes affected
MRAP2 (HGNC:21232): (melanocortin 2 receptor accessory protein 2) This gene encodes a protein that modulates melanocortin receptor signaling. The encoded protein has been shown to interact with all known melanocortin receptors and may regulate both receptor trafficking and activation in response to ligands. Mice lacking a functional copy of this gene exhibit severe obesity and a mutation in this gene may be associated with severe obesity in human patients. [provided by RefSeq, Oct 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons MANE Protein UniProt
MRAP2NM_138409.4 linkuse as main transcriptc.70G>A p.Glu24Lys missense_variant 2/4 ENST00000257776.5 NP_612418.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MRAP2ENST00000257776.5 linkuse as main transcriptc.70G>A p.Glu24Lys missense_variant 2/41 NM_138409.4 ENSP00000257776 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250806
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135520
show subpopulations
Gnomad AFR exome
AF:
0.0000616
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461150
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726872
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Uncertain
0.033
T
BayesDel_noAF
Uncertain
-0.010
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.094
T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.041
D
MetaRNN
Uncertain
0.53
D
MetaSVM
Uncertain
0.071
D
MutationAssessor
Benign
1.2
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-2.0
N
REVEL
Uncertain
0.52
Sift
Benign
0.065
T
Sift4G
Benign
0.11
T
Polyphen
0.83
P
Vest4
0.67
MutPred
0.38
Gain of methylation at E24 (P = 5e-04);
MVP
0.42
MPC
0.42
ClinPred
0.85
D
GERP RS
5.6
Varity_R
0.30
gMVP
0.75

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: rs587777046; hg19: chr6-84765107; COSMIC: COSV57632384; API