13-31758273-A-C

Variant names:

• chr13-31758273-A-C
• rs764255499
• NM_130806.5:c.110A>C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_130806.5(RXFP2):​c.110A>C​(p.Gln37Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: RXFP2 NM_130806.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17420393).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXFP2	NM_130806.5	c.110A>C	p.Gln37Pro	missense_variant	Exon 2 of 18	ENST00000298386.7	NP_570718.1
RXFP2	NM_001166058.2	c.110A>C	p.Gln37Pro	missense_variant	Exon 2 of 17		NP_001159530.1
RXFP2	XM_017020389.2	c.110A>C	p.Gln37Pro	missense_variant	Exon 2 of 15		XP_016875878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXFP2	ENST00000298386.7	c.110A>C	p.Gln37Pro	missense_variant	Exon 2 of 18	1	NM_130806.5	ENSP00000298386.2
RXFP2	ENST00000380314.2	c.110A>C	p.Gln37Pro	missense_variant	Exon 2 of 17	1		ENSP00000369670.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251348 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135840

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461790 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727196

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.110A>C (p.Q37P) alteration is located in exon 2 (coding exon 2) of the RXFP2 gene. This alteration results from a A to C substitution at nucleotide position 110, causing the glutamine (Q) at amino acid position 37 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.45
DEOGEN2	Benign	0.096	.;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.62
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.92	N;N
REVEL	Benign	0.27
Sift	Benign	0.23	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.019	.;B
Vest4		0.38
MutPred		0.46		Gain of catalytic residue at S39 (P = 0);Gain of catalytic residue at S39 (P = 0);
MVP		0.72
MPC		0.21
ClinPred		0.042	T
GERP RS		3.1
Varity_R		0.19
gMVP		0.36

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

Other links and lift over

dbSNP: rs764255499; hg19: chr13-32332410;