rs121918303

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0046 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 26 hom. )

Consequence

RXFP2
NM_130806.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 1.48

Publications

43 publications found

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 Gene-Disease associations (from GenCC):

cryptorchidism
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

RXFP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 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 [Conflicting_classifications_of_pathogenicity]. Clinvar id is 4159.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
RXFP2	NM_130806.5 link	c.664A>C	p.Thr222Pro	missense_variant	Exon 8 of 18	ENST00000298386.7	NP_570718.1
RXFP2	NM_001166058.2 link	c.664A>C	p.Thr222Pro	missense_variant	Exon 8 of 17		NP_001159530.1
RXFP2	XM_017020389.2 link	c.664A>C	p.Thr222Pro	missense_variant	Exon 8 of 15		XP_016875878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXFP2	ENST00000298386.7 link	c.664A>C	p.Thr222Pro	missense_variant	Exon 8 of 18	1	NM_130806.5	ENSP00000298386.2		Q8WXD0-1
RXFP2	ENST00000380314.2 link	c.664A>C	p.Thr222Pro	missense_variant	Exon 8 of 17	1		ENSP00000369670.1		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

GnomAD2 exomes

AF:

0.00458

AC:

1145

AN:

250010

AF XY:

0.00467

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 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

African (AFR)

AF:

0.00108

AC:

AN:

33428

American (AMR)

AF:

0.00457

AC:

204

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

376

AN:

26076

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00278

AC:

239

AN:

86052

European-Finnish (FIN)

AF:

0.00144

AC:

AN:

53306

Middle Eastern (MID)

AF:

0.00579

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00605

AC:

6716

AN:

1110214

Other (OTH)

AF:

0.00599

AC:

361

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

355

709

1064

1418

1773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00460

AC:

701

AN:

152344

Hom.:

Cov.:

AF XY:

0.00501

AC XY:

373

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00106

AC:

AN:

41584

American (AMR)

AF:

0.00954

AC:

146

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0228

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00352

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00569

AC:

387

AN:

68032

Other (OTH)

AF:

0.00710

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

108

144

180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00560

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: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

RXFP2: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Cryptorchidism

Uncertain:1

Aug 01, 2011

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

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

(source)

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

PhyloP100

1.5

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

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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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rs121918303

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over