9-5300176-C-G

Position:

• chr9-5300176-C-G

Variant summary

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

The NM_134441.3(RLN2):​c.480G>C​(p.Lys160Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RLN2 NM_134441.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.105

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]

ACMG classification

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	Protein	UniProt
RLN2	NM_134441.3	c.480G>C	p.Lys160Asn	missense_variant	2/2	ENST00000381627.4	NP_604390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RLN2	ENST00000381627.4	c.480G>C	p.Lys160Asn	missense_variant	2/2	1	NM_134441.3	ENSP00000371040	P1
RLN2	ENST00000416837.1	c.*227G>C		3_prime_UTR_variant	3/3	3		ENSP00000399616

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2024

The c.480G>C (p.K160N) alteration is located in exon 2 (coding exon 2) of the RLN2 gene. This alteration results from a G to C substitution at nucleotide position 480, causing the lysine (K) at amino acid position 160 to be replaced by an asparagine (N). 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	Pathogenic	0.85
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.15
Sift	Benign	0.046	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.086
MutPred		0.79		Loss of methylation at K160 (P = 0.0067);
MVP		0.49
MPC		0.46
ClinPred		0.76	D
GERP RS		1.3
Varity_R		0.23
gMVP		0.050

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: chr9-5300176;