chr17-42761313-C-A

Variant names:

• chr17-42761313-C-A
• rs1457549584
• NM_005854.3:c.52C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005854.3(RAMP2):​c.52C>A​(p.Arg18Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000087 in 1,149,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: RAMP2 NM_005854.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.056 with no splicing effect.

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.52C>A	p.Arg18Arg	synonymous	Exon 1 of 4	NP_005845.2	O60895-1
	RAMP2-AS1	NR_024461.1		n.-56G>T		upstream_gene	N/A
	RAMP2-AS1	NR_024462.1		n.-56G>T		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.52C>A	p.Arg18Arg	synonymous	Exon 1 of 4	ENSP00000253796.3	O60895-1
	RAMP2	ENST00000587142.5	TSL:1	c.52C>A	p.Arg18Arg	synonymous	Exon 1 of 4	ENSP00000466455.1	O60895-2
	RAMP2	ENST00000904024.1		c.52C>A	p.Arg18Arg	synonymous	Exon 1 of 4	ENSP00000574083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.70e-7 AC: 1 AN: 1149842 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 556222

African (AFR) AF: 0.00 AC: 0 AN: 23150

American (AMR) AF: 0.00 AC: 0 AN: 9668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16312

East Asian (EAS) AF: 0.00 AC: 0 AN: 26056

South Asian (SAS) AF: 0.00 AC: 0 AN: 43966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3138

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 955206

Other (OTH) AF: 0.00 AC: 0 AN: 46688

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.0
DANN	Benign	0.55
PhyloP100		0.056
PromoterAI		-0.067	Neutral

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: rs1457549584; hg19: chr17-40913331;