5-173318056-G-A

Variant names:

Variant summary

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

The NM_003714.3(STC2):c.700C>T(p.Leu234Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,609,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

STC2
NM_003714.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.546

Variant links:

Genes affected

STC2 (HGNC:11374): (stanniocalcin 2) This gene encodes a secreted, homodimeric glycoprotein that is expressed in a wide variety of tissues and may have autocrine or paracrine functions. The encoded protein has 10 of its 15 cysteine residues conserved among stanniocalcin family members and is phosphorylated by casein kinase 2 exclusively on its serine residues. Its C-terminus contains a cluster of histidine residues which may interact with metal ions. The protein may play a role in the regulation of renal and intestinal calcium and phosphate transport, cell metabolism, or cellular calcium/phosphate homeostasis. Constitutive overexpression of human stanniocalcin 2 in mice resulted in pre- and postnatal growth restriction, reduced bone and skeletal muscle growth, and organomegaly. Expression of this gene is induced by estrogen and altered in some breast cancers. [provided by RefSeq, Jul 2008]

STC2 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=0.029510796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STC2	NM_003714.3 link	c.700C>T	p.Leu234Phe	missense_variant	Exon 4 of 4	ENST00000265087.9	NP_003705.1	O76061Q6FHC9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STC2	ENST00000265087.9 link	c.700C>T	p.Leu234Phe	missense_variant	Exon 4 of 4	1	NM_003714.3	ENSP00000265087.4		O76061
STC2	ENST00000520593.1 link	n.*122C>T		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000362

AC:

AN:

248832

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

134588

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000494

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1457756

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724814

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152050

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.700C>T (p.L234F) alteration is located in exon 4 (coding exon 4) of the STC2 gene. This alteration results from a C to T substitution at nucleotide position 700, causing the leucine (L) at amino acid position 234 to be replaced by a phenylalanine (F). 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

0.068

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.11

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.56

M_CAP

Benign

0.0069

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.57

REVEL

Benign

0.10

Sift

Benign

0.23

Sift4G

Benign

0.22

Polyphen

0.26

Vest4

0.044

MutPred

0.62

Gain of methylation at K233 (P = 0.0276);

MVP

0.014

MPC

0.52

ClinPred

0.024

GERP RS

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.025

gMVP

0.16

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