13-31758419-C-T

Variant names:

• chr13-31758419-C-T
• rs61946567
• NM_130806.5:c.241+15C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_130806.5(RXFP2):​c.241+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,613,246 control chromosomes in the GnomAD database, including 25,566 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2478 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23088 hom.)
• Consequence: RXFP2 NM_130806.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.377
• Publications: 7 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-31758419-C-T is Benign according to our data. Variant chr13-31758419-C-T is described in ClinVar as [Benign]. Clinvar id is 1229034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXFP2	NM_130806.5	c.241+15C>T		intron_variant	Intron 2 of 17	ENST00000298386.7	NP_570718.1
RXFP2	NM_001166058.2	c.241+15C>T		intron_variant	Intron 2 of 16		NP_001159530.1
RXFP2	XM_017020389.2	c.241+15C>T		intron_variant	Intron 2 of 14		XP_016875878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXFP2	ENST00000298386.7	c.241+15C>T		intron_variant	Intron 2 of 17	1	NM_130806.5	ENSP00000298386.2
RXFP2	ENST00000380314.2	c.241+15C>T		intron_variant	Intron 2 of 16	1		ENSP00000369670.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27725 AN: 151912 Hom.: 2478 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.192

GnomAD2 exomes AF: 0.189 AC: 47577 AN: 251180 AF XY: 0.192

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.182

Gnomad ASJ exome AF: 0.210

Gnomad EAS exome AF: 0.242

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.200

GnomAD4 exome AF: 0.175 AC: 256090 AN: 1461212 Hom.: 23088 Cov.: 33 AF XY: 0.177 AC XY: 128779 AN XY: 726922

African (AFR) AF: 0.173 AC: 5798 AN: 33462

American (AMR) AF: 0.180 AC: 8035 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 5629 AN: 26126

East Asian (EAS) AF: 0.235 AC: 9344 AN: 39686

South Asian (SAS) AF: 0.219 AC: 18871 AN: 86238

European-Finnish (FIN) AF: 0.200 AC: 10693 AN: 53380

Middle Eastern (MID) AF: 0.232 AC: 1336 AN: 5750

European-Non Finnish (NFE) AF: 0.167 AC: 185432 AN: 1111500

Other (OTH) AF: 0.181 AC: 10952 AN: 60358

GnomAD4 genome AF: 0.182 AC: 27742 AN: 152034 Hom.: 2478 Cov.: 32 AF XY: 0.184 AC XY: 13657 AN XY: 74326

African (AFR) AF: 0.179 AC: 7410 AN: 41468

American (AMR) AF: 0.171 AC: 2615 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 760 AN: 3472

East Asian (EAS) AF: 0.227 AC: 1170 AN: 5158

South Asian (SAS) AF: 0.237 AC: 1143 AN: 4826

European-Finnish (FIN) AF: 0.204 AC: 2150 AN: 10562

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11762 AN: 67956

Other (OTH) AF: 0.192 AC: 405 AN: 2110

Alfa AF: 0.178 Hom.: 475

Bravo AF: 0.181

Asia WGS AF: 0.237 AC: 824 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.70
DANN	Benign	0.52
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61946567; hg19: chr13-32332556; COSMIC: COSV53633146;