13-31777398-A-G

Position:

• chr13-31777398-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130806.5(RXFP2):​c.664A>G​(p.Thr222Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,486 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. 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. T222P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RXFP2 NM_130806.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21665353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXFP2	NM_130806.5	c.664A>G	p.Thr222Ala	missense_variant	8/18	ENST00000298386.7
RXFP2	NM_001166058.2	c.664A>G	p.Thr222Ala	missense_variant	8/17
RXFP2	XM_017020389.2	c.664A>G	p.Thr222Ala	missense_variant	8/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXFP2	ENST00000298386.7	c.664A>G	p.Thr222Ala	missense_variant	8/18	1	NM_130806.5	P1
RXFP2	ENST00000380314.2	c.664A>G	p.Thr222Ala	missense_variant	8/17	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250010 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135106

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459486 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726054

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.14	.;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.18	T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	0.63	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.027
Sift	Benign	0.26	T;T
Sift4G	Benign	0.42	T;T
Polyphen		0.0010	.;B
Vest4		0.20
MutPred		0.42		Gain of catalytic residue at R227 (P = 0.0029);Gain of catalytic residue at R227 (P = 0.0029);
MVP		0.83
MPC		0.17
ClinPred		0.14	T
GERP RS		3.8
Varity_R		0.087
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs121918303; hg19: chr13-32351535;