17-42761301-C-T

Variant names:

• chr17-42761301-C-T
• rs1156806208
• NM_005854.3:c.40C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005854.3(RAMP2):​c.40C>T​(p.Leu14Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAMP2 NM_005854.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0540
• Publications: 0 publications found

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

ACMG classification

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=0.1262762).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAMP2	NM_005854.3	MANE Select	c.40C>T	p.Leu14Phe	missense	Exon 1 of 4	NP_005845.2	O60895-1
	RAMP2-AS1	NR_024461.1		n.-44G>A		upstream_gene	N/A
	RAMP2-AS1	NR_024462.1		n.-44G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAMP2	ENST00000253796.10	TSL:1 MANE Select	c.40C>T	p.Leu14Phe	missense	Exon 1 of 4	ENSP00000253796.3	O60895-1
	RAMP2	ENST00000587142.5	TSL:1	c.40C>T	p.Leu14Phe	missense	Exon 1 of 4	ENSP00000466455.1	O60895-2
	RAMP2	ENST00000904024.1		c.40C>T	p.Leu14Phe	missense	Exon 1 of 4	ENSP00000574083.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152082 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1246358 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 610660

African (AFR) AF: 0.00 AC: 0 AN: 24810

American (AMR) AF: 0.00 AC: 0 AN: 16248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20068

East Asian (EAS) AF: 0.00 AC: 0 AN: 27228

South Asian (SAS) AF: 0.00 AC: 0 AN: 58646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3628

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1014456

Other (OTH) AF: 0.00 AC: 0 AN: 51342

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152192 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74410

African (AFR) AF: 0.00 AC: 0 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.054
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.029
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0030	B
Vest4		0.11
MutPred		0.24		Gain of methylation at R13 (P = 0.1298)
MVP		0.26
MPC		0.47
ClinPred		0.60	D
GERP RS		-1.2
PromoterAI		-0.030	Neutral
Varity_R		0.12
gMVP		0.37

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: rs1156806208; hg19: chr17-40913319;