Variant 2-119452057-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000019103.8(SCTR):c.874G>A(p.Ala292Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 1,608,034 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 30 hom. )

Consequence

SCTR
ENST00000019103.8 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0290

Variant links:

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]

SCTR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034151971).

BP6

Variant 2-119452057-C-T is Benign according to our data. Variant chr2-119452057-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 710544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00408 (5933/1455720) while in subpopulation MID AF= 0.0262 (151/5754). AF 95% confidence interval is 0.0228. There are 30 homozygotes in gnomad4_exome. There are 2985 alleles in male gnomad4_exome subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCTR	NM_002980.3 linkuse as main transcript	c.874G>A	p.Ala292Thr	missense_variant	9/13	ENST00000019103.8	NP_002971.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCTR	ENST00000019103.8 linkuse as main transcript	c.874G>A	p.Ala292Thr	missense_variant	9/13	1	NM_002980.3	ENSP00000019103	P1
SCTR	ENST00000485440.1 linkuse as main transcript	n.1554G>A		non_coding_transcript_exon_variant	6/10	2

Frequencies

GnomAD3 genomes

AF:

0.00378

AC:

575

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00289

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00517

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00375

AC:

916

AN:

243946

Hom.:

AF XY:

0.00396

AC XY:

520

AN XY:

131316

show subpopulations

Gnomad AFR exome

AF:

0.000509

Gnomad AMR exome

AF:

0.00311

Gnomad ASJ exome

AF:

0.00658

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00324

Gnomad FIN exome

AF:

0.000568

Gnomad NFE exome

AF:

0.00540

Gnomad OTH exome

AF:

0.00613

GnomAD4 exome

AF:

0.00408

AC:

5933

AN:

1455720

Hom.:

Cov.:

AF XY:

0.00412

AC XY:

2985

AN XY:

723914

show subpopulations

Gnomad4 AFR exome

AF:

0.000958

Gnomad4 AMR exome

AF:

0.00324

Gnomad4 ASJ exome

AF:

0.00715

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00342

Gnomad4 FIN exome

AF:

0.000526

Gnomad4 NFE exome

AF:

0.00434

Gnomad4 OTH exome

AF:

0.00483

GnomAD4 genome

AF:

0.00378

AC:

575

AN:

152314

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

249

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00517

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00527

Hom.:

Bravo

AF:

0.00417

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00523

AC:

ExAC

AF:

0.00402

AC:

488

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

6.0

DANN

Benign

0.61

DEOGEN2

Benign

0.065

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.18

M_CAP

Benign

0.0077

MetaRNN

Benign

0.0034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.040

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

0.55

REVEL

Benign

0.038

Sift

Benign

0.84

Sift4G

Benign

0.55

Polyphen

0.0010

Vest4

0.31

MVP

0.32

MPC

0.093

ClinPred

0.00087

GERP RS

1.4

Varity_R

0.023

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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