dbSNP rs1240242901: RAMP2:p.Arg13Gly (chr17-42761298-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005854.3(RAMP2):c.37C>G(p.Arg13Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,242,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

RAMP2
NM_005854.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.101

Publications

0 publications found

Variant links:

Genes affected

RAMP2 (HGNC:9844): (receptor activity modifying protein 2) The protein encoded by this gene is a member of the RAMP family of single-transmembrane-domain proteins, called receptor (calcitonin) activity modifying proteins (RAMPs). RAMPs are type I transmembrane proteins with an extracellular N terminus and a cytoplasmic C terminus. RAMPs are required to transport calcitonin-receptor-like receptor (CRLR) to the plasma membrane. CRLR, a receptor with seven transmembrane domains, can function as either a calcitonin-gene-related peptide (CGRP) receptor or an adrenomedullin receptor, depending on which members of the RAMP family are expressed. In the presence of this (RAMP2) protein, CRLR functions as an adrenomedullin receptor. The RAMP2 protein is involved in core glycosylation and transportation of adrenomedullin receptor to the cell surface. [provided by RefSeq, Jul 2008]

RAMP2 links:

RAMP2-AS1 (HGNC:44358): (RAMP2 antisense RNA 1)

RAMP2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1802308).

BS2

High AC in GnomAdExome4 at 16 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005854.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAMP2	NM_005854.3	MANE Select	c.37C>G	p.Arg13Gly	missense	Exon 1 of 4	NP_005845.2	O60895-1
RAMP2-AS1	NR_024461.1		n.-41G>C		upstream_gene	N/A
RAMP2-AS1	NR_024462.1		n.-41G>C		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAMP2	ENST00000253796.10	TSL:1 MANE Select	c.37C>G	p.Arg13Gly	missense	Exon 1 of 4	ENSP00000253796.3	O60895-1
RAMP2	ENST00000587142.5	TSL:1	c.37C>G	p.Arg13Gly	missense	Exon 1 of 4	ENSP00000466455.1	O60895-2
RAMP2	ENST00000904024.1		c.37C>G	p.Arg13Gly	missense	Exon 1 of 4	ENSP00000574083.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000129

AC:

AN:

1242384

Hom.:

Cov.:

AF XY:

0.0000164

AC XY:

AN XY:

608456

show subpopulations

African (AFR)

AF:

0.0000401

AC:

AN:

24930

American (AMR)

AF:

0.00

AC:

AN:

17740

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20096

East Asian (EAS)

AF:

0.00

AC:

AN:

27098

South Asian (SAS)

AF:

0.00

AC:

AN:

58318

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3602

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

1010028

Other (OTH)

AF:

0.00

AC:

AN:

51010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.21

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.41

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.10

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.51

REVEL

Benign

0.031

Sift

Benign

0.080

Sift4G

Benign

0.066

Polyphen

0.65

Vest4

0.14

MutPred

0.20

Loss of methylation at R13 (P = 0.0145)

MVP

0.63

MPC

0.34

ClinPred

0.13

GERP RS

1.5

PromoterAI

0.038

Neutral

(source)

Varity_R

0.11

gMVP

0.41

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over