Genetic Variant RXFP2:c.242-21A>T (chr13-31761703-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_130806.5(RXFP2):c.242-21A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,550,826 control chromosomes in the GnomAD database, including 24,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2345 hom., cov: 33)

Exomes 𝑓: 0.18 ( 22461 hom. )

Consequence

RXFP2
NM_130806.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.428

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 13-31761703-A-T is Benign according to our data. Variant chr13-31761703-A-T is described in ClinVar as [Benign]. Clinvar id is 1268067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
RXFP2	NM_130806.5 link	c.242-21A>T	intron_variant	Intron 2 of 17	ENST00000298386.7	NP_570718.1
RXFP2	NM_001166058.2 link	c.242-21A>T	intron_variant	Intron 2 of 16		NP_001159530.1
RXFP2	XM_017020389.2 link	c.242-21A>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 link	c.242-21A>T		intron_variant	Intron 2 of 17	1	NM_130806.5	ENSP00000298386.2		Q8WXD0-1
RXFP2	ENST00000380314.2 link	c.242-21A>T		intron_variant	Intron 2 of 16	1		ENSP00000369670.1		Q8WXD0-2

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26875

AN:

152080

Hom.:

2346

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.187

GnomAD3 exomes

AF:

0.188

AC:

47127

AN:

250900

Hom.:

4455

AF XY:

0.191

AC XY:

25918

AN XY:

135590

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.181

Gnomad ASJ exome

AF:

0.210

Gnomad EAS exome

AF:

0.241

Gnomad SAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.174

Gnomad OTH exome

AF:

0.199

GnomAD4 exome

AF:

0.177

AC:

246878

AN:

1398628

Hom.:

22461

Cov.:

AF XY:

0.178

AC XY:

124752

AN XY:

699598

show subpopulations

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.216

Gnomad4 EAS exome

AF:

0.236

Gnomad4 SAS exome

AF:

0.219

Gnomad4 FIN exome

AF:

0.200

Gnomad4 NFE exome

AF:

0.169

Gnomad4 OTH exome

AF:

0.181

GnomAD4 genome

AF:

0.177

AC:

26877

AN:

152198

Hom.:

2345

Cov.:

AF XY:

0.178

AC XY:

13234

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.168

Gnomad4 ASJ

AF:

0.218

Gnomad4 EAS

AF:

0.227

Gnomad4 SAS

AF:

0.236

Gnomad4 FIN

AF:

0.204

Gnomad4 NFE

AF:

0.173

Gnomad4 OTH

AF:

0.187

Alfa

AF:

0.175

Hom.:

450

Bravo

AF:

0.175

Asia WGS

AF:

0.233

AC:

807

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

-0.78

CADD

Benign

0.18

DANN

Benign

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over