chr9-5304505-A-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_134441.3(RLN2):c.76T>A(p.Ser26Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000955 in 1,613,070 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00024 ( 1 hom., cov: 28)
Exomes 𝑓: 0.000080 ( 4 hom. )
Consequence
RLN2
NM_134441.3 missense
NM_134441.3 missense
Scores
19
Clinical Significance
Conservation
PhyloP100: -0.711
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 Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.04188323).
BS2
?
High Homozygotes in GnomAdExome4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RLN2 | NM_134441.3 | c.76T>A | p.Ser26Thr | missense_variant | 1/2 | ENST00000381627.4 | |
RLN2 | NM_005059.4 | c.76T>A | p.Ser26Thr | missense_variant | 1/3 | ||
RLN2 | XM_047423707.1 | c.28T>A | p.Ser10Thr | missense_variant | 4/5 | ||
RLN2 | XM_047423709.1 | c.-45+1168T>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RLN2 | ENST00000381627.4 | c.76T>A | p.Ser26Thr | missense_variant | 1/2 | 1 | NM_134441.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000244 AC: 37AN: 151878Hom.: 1 Cov.: 28
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251362Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135844
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GnomAD4 exome AF: 0.0000801 AC: 117AN: 1461078Hom.: 4 Cov.: 31 AF XY: 0.0000839 AC XY: 61AN XY: 726848
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GnomAD4 genome ? AF: 0.000243 AC: 37AN: 151992Hom.: 1 Cov.: 28 AF XY: 0.000215 AC XY: 16AN XY: 74298
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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 | Dec 28, 2023 | The c.76T>A (p.S26T) alteration is located in exon 1 (coding exon 1) of the RLN2 gene. This alteration results from a T to A substitution at nucleotide position 76, causing the serine (S) at amino acid position 26 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at