Genetic Variant NM_005854.3:c.37C>T (chr17-42761298-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005854.3(RAMP2):c.37C>T(p.Arg13Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. R13G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RAMP2
NM_005854.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23487535).

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>T	p.Arg13Cys	missense	Exon 1 of 4	NP_005845.2	O60895-1
RAMP2-AS1	NR_024461.1		n.-41G>A		upstream_gene	N/A
RAMP2-AS1	NR_024462.1		n.-41G>A		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>T	p.Arg13Cys	missense	Exon 1 of 4	ENSP00000253796.3	O60895-1
RAMP2	ENST00000587142.5	TSL:1	c.37C>T	p.Arg13Cys	missense	Exon 1 of 4	ENSP00000466455.1	O60895-2
RAMP2	ENST00000904024.1		c.37C>T	p.Arg13Cys	missense	Exon 1 of 4	ENSP00000574083.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

45152

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1242384

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

608456

African (AFR)

AF:

0.00

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:

0.00

AC:

AN:

1010028

Other (OTH)

AF:

0.00

AC:

AN:

51010

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.21

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.10

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.36

REVEL

Benign

0.073

Sift

Benign

0.061

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.16

MutPred

0.36

Gain of catalytic residue at P12 (P = 0.0059)

MVP

0.66

MPC

0.57

ClinPred

0.51

GERP RS

1.5

PromoterAI

-0.0025

Neutral

(source)

Varity_R

0.097

gMVP

0.32

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over