17-73169882-G-C

Position:

• chr17-73169882-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001050.3(SSTR2):​c.563G>C​(p.Trp188Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SSTR2 NM_001050.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.876

Genes affected

SSTR2 (HGNC:11331): (somatostatin receptor 2) Somatostatin acts at many sites to inhibit the release of many hormones and other secretory proteins. The biologic effects of somatostatin are probably mediated by a family of G protein-coupled receptors that are expressed in a tissue-specific manner. SSTR2 is a member of the superfamily of receptors having seven transmembrane segments and is expressed in highest levels in cerebrum and kidney. [provided by RefSeq, Jul 2008]

ENSG00000264860 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09473148).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSTR2	NM_001050.3	c.563G>C	p.Trp188Ser	missense_variant	2/2	ENST00000357585.4	NP_001041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSTR2	ENST00000357585.4	c.563G>C	p.Trp188Ser	missense_variant	2/2	1	NM_001050.3	ENSP00000350198.2
ENSG00000264860	ENST00000580671.1	n.312+4594G>C		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

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

Aug 20, 2024

The c.563G>C (p.W188S) alteration is located in exon 2 (coding exon 1) of the SSTR2 gene. This alteration results from a G to C substitution at nucleotide position 563, causing the tryptophan (W) at amino acid position 188 to be replaced by a serine (S). 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	0.12
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Benign	0.89
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.63	N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.15
Sift	Benign	0.68	T
Sift4G	Benign	0.79	T
Polyphen		0.0010	B
Vest4		0.26
MutPred		0.52		Gain of disorder (P = 0);
MVP		0.69
MPC		0.45
ClinPred		0.12	T
GERP RS		4.1
Varity_R		0.11
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs1001497716; hg19: chr17-71166021;