Genetic Variant RXFP2:c.241+120T>C (chr13-31758524-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_130806.5(RXFP2):c.241+120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 1,159,644 control chromosomes in the GnomAD database, including 246,660 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.67 ( 33774 hom., cov: 32)

Exomes 𝑓: 0.65 ( 212886 hom. )

Consequence

RXFP2
NM_130806.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.674

Publications

3 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

RXFP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 13-31758524-T-C is Benign according to our data. Variant chr13-31758524-T-C is described in ClinVar as [Benign]. Clinvar id is 1283483.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
RXFP2	NM_130806.5 link	c.241+120T>C	intron_variant	Intron 2 of 17	ENST00000298386.7	NP_570718.1
RXFP2	NM_001166058.2 link	c.241+120T>C	intron_variant	Intron 2 of 16		NP_001159530.1
RXFP2	XM_017020389.2 link	c.241+120T>C	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.241+120T>C		intron_variant	Intron 2 of 17	1	NM_130806.5	ENSP00000298386.2		Q8WXD0-1
RXFP2	ENST00000380314.2 link	c.241+120T>C		intron_variant	Intron 2 of 16	1		ENSP00000369670.1		Q8WXD0-2

Frequencies

GnomAD3 genomes

AF:

0.666

AC:

101209

AN:

151962

Hom.:

33737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.666

Gnomad AMI

AF:

0.683

Gnomad AMR

AF:

0.717

Gnomad ASJ

AF:

0.697

Gnomad EAS

AF:

0.522

Gnomad SAS

AF:

0.617

Gnomad FIN

AF:

0.725

Gnomad MID

AF:

0.668

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.676

GnomAD4 exome

AF:

0.647

AC:

651585

AN:

1007564

Hom.:

212886

AF XY:

0.646

AC XY:

329207

AN XY:

509648

show subpopulations

African (AFR)

AF:

0.662

AC:

16064

AN:

24260

American (AMR)

AF:

0.750

AC:

26980

AN:

35954

Ashkenazi Jewish (ASJ)

AF:

0.680

AC:

13525

AN:

19890

East Asian (EAS)

AF:

0.523

AC:

19221

AN:

36746

South Asian (SAS)

AF:

0.628

AC:

41983

AN:

66882

European-Finnish (FIN)

AF:

0.722

AC:

34266

AN:

47470

Middle Eastern (MID)

AF:

0.679

AC:

2071

AN:

3052

European-Non Finnish (NFE)

AF:

0.643

AC:

468206

AN:

728518

Other (OTH)

AF:

0.653

AC:

29269

AN:

44792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

10705

21410

32114

42819

53524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.666

AC:

101290

AN:

152080

Hom.:

33774

Cov.:

AF XY:

0.668

AC XY:

49624

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.667

AC:

27652

AN:

41484

American (AMR)

AF:

0.717

AC:

10961

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.697

AC:

2418

AN:

3470

East Asian (EAS)

AF:

0.522

AC:

2693

AN:

5162

South Asian (SAS)

AF:

0.616

AC:

2972

AN:

4824

European-Finnish (FIN)

AF:

0.725

AC:

7663

AN:

10568

Middle Eastern (MID)

AF:

0.677

AC:

199

AN:

294

European-Non Finnish (NFE)

AF:

0.658

AC:

44688

AN:

67966

Other (OTH)

AF:

0.674

AC:

1421

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1739

3477

5216

6954

8693

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.668

Hom.:

11629

Bravo

AF:

0.668

Asia WGS

AF:

0.596

AC:

2072

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

4.6

(source)

DANN

Benign

0.29

PhyloP100

0.67

Mutation Taster

=100/0

polymorphism (auto)

(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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13-31758524-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over