Genetic Variant RXFP2:p.Ser84Ile (chr13-31761733-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_130806.5(RXFP2):c.251G>T(p.Ser84Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S84N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RXFP2
NM_130806.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.68

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
RXFP2	NM_130806.5 link	c.251G>T	p.Ser84Ile	missense_variant	Exon 3 of 18	ENST00000298386.7	NP_570718.1
RXFP2	NM_001166058.2 link	c.251G>T	p.Ser84Ile	missense_variant	Exon 3 of 17		NP_001159530.1
RXFP2	XM_017020389.2 link	c.251G>T	p.Ser84Ile	missense_variant	Exon 3 of 15		XP_016875878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXFP2	ENST00000298386.7 link	c.251G>T	p.Ser84Ile	missense_variant	Exon 3 of 18	1	NM_130806.5	ENSP00000298386.2		Q8WXD0-1
RXFP2	ENST00000380314.2 link	c.251G>T	p.Ser84Ile	missense_variant	Exon 3 of 17	1		ENSP00000369670.1		Q8WXD0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725936

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33426

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.00

AC:

AN:

86212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1109404

Other (OTH)

AF:

0.00

AC:

AN:

60268

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.19

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

.;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.9

L;L

PhyloP100

5.7

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.1

D;D

REVEL

Uncertain

0.41

Sift

Benign

0.074

T;T

Sift4G

Uncertain

0.010

D;D

Polyphen

0.35

.;B

Vest4

0.65

MutPred

0.47

Gain of catalytic residue at A87 (P = 0);Gain of catalytic residue at A87 (P = 0);

MVP

0.90

MPC

0.23

ClinPred

0.95

GERP RS

5.8

Varity_R

0.39

gMVP

0.51

Mutation Taster

=59/41

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr13-31761733-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over