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GeneBe

9-5300316-G-C

Variant summary

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

The NM_134441.3(RLN2):c.340C>G(p.Gln114Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,150 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RLN2
NM_134441.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.575
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RLN2NM_134441.3 linkuse as main transcriptc.340C>G p.Gln114Glu missense_variant 2/2 ENST00000381627.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RLN2ENST00000381627.4 linkuse as main transcriptc.340C>G p.Gln114Glu missense_variant 2/21 NM_134441.3 P1P04090-1
RLN2ENST00000416837.1 linkuse as main transcriptc.*87C>G 3_prime_UTR_variant 3/33

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461150
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726922
show subpopulations
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:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 submitterclinical testingAmbry GeneticsMay 09, 2023The c.340C>G (p.Q114E) alteration is located in exon 2 (coding exon 2) of the RLN2 gene. This alteration results from a C to G substitution at nucleotide position 340, causing the glutamine (Q) at amino acid position 114 to be replaced by a glutamic acid (E). 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
0.074
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
Cadd
Benign
15
Dann
Benign
0.96
DEOGEN2
Benign
0.21
T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.46
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.55
T
M_CAP
Benign
0.0024
T
MetaRNN
Uncertain
0.44
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Uncertain
2.6
M
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.70
N
REVEL
Benign
0.20
Sift
Benign
0.10
T
Sift4G
Benign
1.0
T
Polyphen
1.0
D
Vest4
0.17
MutPred
0.76
Gain of catalytic residue at Q114 (P = 0.2984);
MVP
0.53
MPC
0.43
ClinPred
0.30
T
GERP RS
0.044
Varity_R
0.11
gMVP
0.024

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-5300316; API