Variant rs121918303 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_130806.5(RXFP2):c.664A>C(p.Thr222Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00542 in 1,611,690 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 26 hom. )

Consequence

RXFP2
NM_130806.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 1.48

Variant links:

Genes affected

RXFP2 (HGNC:17318): (relaxin family peptide receptor 2) This gene encodes a member of the GPCR (G protein-coupled, 7-transmembrane receptor) family. Mutations in this gene are associated with cryptorchidism. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

RXFP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011102617).

BP6

Variant 13-31777398-A-C is Benign according to our data. Variant chr13-31777398-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 4159.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 701 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RXFP2	NM_130806.5 linkuse as main transcript	c.664A>C	p.Thr222Pro	missense_variant	8/18	ENST00000298386.7
RXFP2	NM_001166058.2 linkuse as main transcript	c.664A>C	p.Thr222Pro	missense_variant	8/17
RXFP2	XM_017020389.2 linkuse as main transcript	c.664A>C	p.Thr222Pro	missense_variant	8/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXFP2	ENST00000298386.7 linkuse as main transcript	c.664A>C	p.Thr222Pro	missense_variant	8/18	1	NM_130806.5	P1	Q8WXD0-1
RXFP2	ENST00000380314.2 linkuse as main transcript	c.664A>C	p.Thr222Pro	missense_variant	8/17	1			Q8WXD0-2

Frequencies

GnomAD3 genomes

AF:

0.00460

AC:

700

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00956

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00569

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00458

AC:

1145

AN:

250010

Hom.:

AF XY:

0.00467

AC XY:

631

AN XY:

135106

show subpopulations

Gnomad AFR exome

AF:

0.000990

Gnomad AMR exome

AF:

0.00483

Gnomad ASJ exome

AF:

0.0137

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00299

Gnomad FIN exome

AF:

0.00181

Gnomad NFE exome

AF:

0.00579

Gnomad OTH exome

AF:

0.00690

GnomAD4 exome

AF:

0.00551

AC:

8042

AN:

1459346

Hom.:

Cov.:

AF XY:

0.00543

AC XY:

3941

AN XY:

725978

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00457

Gnomad4 ASJ exome

AF:

0.0144

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00278

Gnomad4 FIN exome

AF:

0.00144

Gnomad4 NFE exome

AF:

0.00605

Gnomad4 OTH exome

AF:

0.00599

GnomAD4 genome

AF:

0.00460

AC:

701

AN:

152344

Hom.:

Cov.:

AF XY:

0.00501

AC XY:

373

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00954

Gnomad4 ASJ

AF:

0.0228

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00569

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00587

Hom.:

Bravo

AF:

0.00463

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00617

AC:

ExAC

AF:

0.00440

AC:

534

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00715

EpiControl

AF:

0.00748

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cryptorchidism

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Aug 01, 2011

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

RXFP2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

.;T

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.20

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.52

MutationAssessor

Pathogenic

3.1

M;M

MutationTaster

Benign

0.75

A;A

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.22

Sift

Uncertain

0.025

D;T

Sift4G

Benign

0.12

T;T

Polyphen

0.74

.;P

Vest4

0.44

MVP

0.89

MPC

0.38

ClinPred

0.060

GERP RS

3.8

Varity_R

0.32

gMVP

0.71

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over