Genetic Variant NM_130806.5:c.251G>C (chr13-31761733-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_130806.5(RXFP2):c.251G>C(p.Ser84Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,886 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. 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: 0.0000014 ( 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
disorder of sexual differentiation
Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

RXFP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26829684).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130806.5. 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
	RXFP2	NM_130806.5	MANE Select	c.251G>C	p.Ser84Thr	missense	Exon 3 of 18	NP_570718.1	Q8WXD0-1
	RXFP2	NM_001166058.2		c.251G>C	p.Ser84Thr	missense	Exon 3 of 17	NP_001159530.1	Q8WXD0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXFP2	ENST00000298386.7	TSL:1 MANE Select	c.251G>C	p.Ser84Thr	missense	Exon 3 of 18	ENSP00000298386.2	Q8WXD0-1
	RXFP2	ENST00000380314.2	TSL:1	c.251G>C	p.Ser84Thr	missense	Exon 3 of 17	ENSP00000369670.1	Q8WXD0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725936

show subpopulations

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:

0.0000116

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:

0.00

AC:

AN:

1109404

Other (OTH)

AF:

0.0000166

AC:

AN:

60268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.74

M_CAP

Benign

0.016

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.6

PhyloP100

5.7

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.91

REVEL

Benign

0.16

Sift

Benign

0.74

Sift4G

Benign

0.41

Polyphen

0.23

Vest4

0.45

MutPred

0.35

Gain of catalytic residue at A87 (P = 0)

MVP

0.88

MPC

0.18

ClinPred

0.89

GERP RS

5.8

Varity_R

0.21

gMVP

0.37

Mutation Taster

=73/27

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over