2-119461867-C-T

Variant names:

• chr2-119461867-C-T
• NM_002980.3:c.770G>A

Variant summary

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

The NM_002980.3(SCTR):​c.770G>A​(p.Gly257Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCTR NM_002980.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.09

Genes affected

SCTR (HGNC:10608): (secretin receptor) The protein encoded by this gene is a G protein-coupled receptor and belongs to the glucagon-VIP-secretin receptor family. It binds secretin which is the most potent regulator of pancreatic bicarbonate, electrolyte and volume secretion. Secretin and its receptor are suggested to be involved in pancreatic cancer and autism. [provided by RefSeq, Jul 2008]

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 rank	MANE	Protein	UniProt
SCTR	NM_002980.3	c.770G>A	p.Gly257Glu	missense_variant	Exon 7 of 13	ENST00000019103.8	NP_002971.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCTR	ENST00000019103.8	c.770G>A	p.Gly257Glu	missense_variant	Exon 7 of 13	1	NM_002980.3	ENSP00000019103.6
SCTR	ENST00000485440.1	n.1450G>A		non_coding_transcript_exon_variant	Exon 4 of 10	2
SCTR	ENST00000627145.1	c.*116G>A		downstream_gene_variant		5		ENSP00000486987.1
SCTR	ENST00000630739.2	c.*116G>A		downstream_gene_variant		5		ENSP00000486930.1

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

Nov 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.770G>A (p.G257E) alteration is located in exon 7 (coding exon 7) of the SCTR gene. This alteration results from a G to A substitution at nucleotide position 770, causing the glycine (G) at amino acid position 257 to be replaced by a glutamic acid (E). 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	0.30
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0050	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.13
Sift	Benign	0.24	T
Sift4G	Benign	0.27	T
Polyphen		0.0010	B
Vest4		0.43
MutPred		0.75		Gain of ubiquitination at K253 (P = 0.0913);
MVP		0.56
MPC		0.13
ClinPred		0.29	T
GERP RS		2.2
Varity_R		0.18
gMVP		0.56

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: chr2-120219443; COSMIC: COSV99191508; COSMIC: COSV99191508;