2-119461998-C-T

Position:

• chr2-119461998-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_002980.3(SCTR):​c.639G>A​(p.Ala213=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000205 in 1,598,800 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (5 hom.)
• Consequence: SCTR NM_002980.3 splice_region, synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0410

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 2-119461998-C-T is Benign according to our data. Variant chr2-119461998-C-T is described in ClinVar as [Benign]. Clinvar id is 717175.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCTR	NM_002980.3	c.639G>A	p.Ala213=	splice_region_variant, synonymous_variant	7/13	ENST00000019103.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCTR	ENST00000019103.8	c.639G>A	p.Ala213=	splice_region_variant, synonymous_variant	7/13	1	NM_002980.3	P1
SCTR	ENST00000627145.1	c.714G>A	p.Ala238=	splice_region_variant, synonymous_variant	8/8	5
SCTR	ENST00000630739.2	c.435G>A	p.Ala145=	splice_region_variant, synonymous_variant	8/8	5
SCTR	ENST00000485440.1	n.1319G>A		splice_region_variant, non_coding_transcript_exon_variant	4/10	2

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000642 AC: 154 AN: 239748 Hom.: 2 AF XY: 0.000571 AC XY: 74 AN XY: 129608

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00466

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000106

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000914

Gnomad OTH exome AF: 0.000174

GnomAD4 exome AF: 0.000196 AC: 283 AN: 1446524 Hom.: 5 Cov.: 31 AF XY: 0.000188 AC XY: 135 AN XY: 718946

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00528

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000598

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000181

Gnomad4 OTH exome AF: 0.000503

GnomAD4 genome AF: 0.000296 AC: 45 AN: 152276 Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21 AN XY: 74452

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000131 Hom.: 0

Bravo AF: 0.000506

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 11, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.85		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.85		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs376416323; hg19: chr2-120219574; COSMIC: COSV50027331;