rs1762448127

Variant names:

• chr5-173318208-T-G
• rs1762448127
• NM_003714.3:c.548A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003714.3(STC2):​c.548A>C​(p.Glu183Ala) variant causes a missense change involving the alteration of a 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)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STC2 NM_003714.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003714.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STC2	NM_003714.3	MANE Select	c.548A>C	p.Glu183Ala	missense	Exon 4 of 4	NP_003705.1	O76061

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STC2	ENST00000265087.9	TSL:1 MANE Select	c.548A>C	p.Glu183Ala	missense	Exon 4 of 4	ENSP00000265087.4	O76061
	STC2	ENST00000520593.1	TSL:4	n.536A>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.31e-7 AC: 1 AN: 1367154 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 672310

African (AFR) AF: 0.00 AC: 0 AN: 30234

American (AMR) AF: 0.00 AC: 0 AN: 31172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20948

East Asian (EAS) AF: 0.00 AC: 0 AN: 38260

South Asian (SAS) AF: 0.00 AC: 0 AN: 71838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50072

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5282

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063548

Other (OTH) AF: 0.0000179 AC: 1 AN: 55800

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.70	D
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.7
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.64		Loss of disorder (P = 0.0649)
MVP		0.17
MPC		1.3
ClinPred		0.99	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.43
gMVP		0.56
Mutation Taster		=44/56	disease causing

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

Other links and lift over

dbSNP: rs1762448127; hg19: chr5-172745211;