6-84055388-G-A

Variant names:

• chr6-84055388-G-A
• rs587777046
• NM_138409.4:c.70G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.31
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138409.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRAP2	NM_138409.4	MANE Select	c.70G>A	p.Glu24Lys	missense	Exon 2 of 4	NP_612418.2
	MRAP2	NM_001346542.2		c.70G>A	p.Glu24Lys	missense	Exon 3 of 5	NP_001333471.1
	MRAP2	NM_001346544.2		c.70G>A	p.Glu24Lys	missense	Exon 2 of 4	NP_001333473.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRAP2	ENST00000257776.5	TSL:1 MANE Select	c.70G>A	p.Glu24Lys	missense	Exon 2 of 4	ENSP00000257776.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250806 AF XY: 0.00

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 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

African (AFR) AF: 0.0000299 AC: 1 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111676

Other (OTH) AF: 0.00 AC: 0 AN: 60362

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		5.3
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
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

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