Variant 9-5300223-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000416837(RLN2):c.*180C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000845 in 1,613,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00086 ( 0 hom. )

Consequence

RLN2
ENST00000416837 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.115

Variant links:

Genes affected

RLN2 (HGNC:10027): (relaxin 2) This gene encodes a member of the relaxin subfamily and insulin superfamily of peptide hormones. In humans there are three non-allelic relaxin genes. This gene encodes multiple protein isoforms, at least one of which undergoes proteolytic processing. This processing generates relaxin A and B chains that are linked by disulfide bonds to form the mature peptide hormone. This hormone plays a role in the male and female reproductive systems and was initially noted for its role in pregnancy. This protein also plays broader roles in the cardiovascular system, including in the regulation of blood pressure and control of heart rate, and data from animal models shows that this protein may have anti-fibrotic and cardioprotective effects. [provided by RefSeq, Jul 2016]

RLN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015596479).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RLN2	NM_134441.3 link	c.433C>T	p.Pro145Ser	missense_variant	2/2	ENST00000381627.4	NP_604390.1	P04090-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RLN2	ENST00000381627.4 link	c.433C>T	p.Pro145Ser	missense_variant	2/2	1	NM_134441.3	ENSP00000371040.3		P04090-1
RLN2	ENST00000416837 link	c.*180C>T		3_prime_UTR_variant	3/3	3		ENSP00000399616.1		H0Y5M9

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000985

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000788

AC:

198

AN:

251376

Hom.:

AF XY:

0.000684

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000954

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000863

AC:

1262

AN:

1461618

Hom.:

Cov.:

AF XY:

0.000839

AC XY:

610

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000984

Gnomad4 ASJ exome

AF:

0.00260

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000954

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.000664

AC:

101

AN:

152206

Hom.:

Cov.:

AF XY:

0.000753

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.000985

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00111

Hom.:

Bravo

AF:

0.000650

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000758

AC:

EpiCase

AF:

0.000764

EpiControl

AF:

0.000948

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.433C>T (p.P145S) alteration is located in exon 2 (coding exon 2) of the RLN2 gene. This alteration results from a C to T substitution at nucleotide position 433, causing the proline (P) at amino acid position 145 to be replaced by a serine (S). 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

0.10

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.34

CADD

Benign

1.3

DANN

Benign

0.19

DEOGEN2

Benign

0.31

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.43

M_CAP

Benign

0.024

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.20

Sift

Benign

0.55

Sift4G

Benign

0.66

Polyphen

0.14

Vest4

0.094

MVP

0.49

MPC

0.080

ClinPred

0.014

GERP RS

2.1

Varity_R

0.064

gMVP

0.072

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