chr2-119452057-C-T

Variant names:

• chr2-119452057-C-T
• rs140893531
• NM_002980.3:c.874G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002980.3(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. 16/22 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 NM_002980.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0290
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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. GnomAdExome4 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 GnomAdExome4. There are 2985 alleles in the male GnomAdExome4 subpopulation. Median coverage is 28. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002980.3. 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
	SCTR	NM_002980.3	MANE Select	c.874G>A	p.Ala292Thr	missense	Exon 9 of 13	NP_002971.2	P47872

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCTR	ENST00000019103.8	TSL:1 MANE Select	c.874G>A	p.Ala292Thr	missense	Exon 9 of 13	ENSP00000019103.6	P47872
	SCTR	ENST00000903274.1		c.1069G>A	p.Ala357Thr	missense	Exon 11 of 15	ENSP00000573333.1
	SCTR	ENST00000903275.1		c.889G>A	p.Ala297Thr	missense	Exon 9 of 13	ENSP00000573334.1

Frequencies

GnomAD3 genomes AF: 0.00378 AC: 575 AN: 152198 Hom.: 4 Cov.: 33

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

GnomAD2 exomes AF: 0.00375 AC: 916 AN: 243946 AF XY: 0.00396

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 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.: 30 Cov.: 28 AF XY: 0.00412 AC XY: 2985 AN XY: 723914

African (AFR) AF: 0.000958 AC: 32 AN: 33398

American (AMR) AF: 0.00324 AC: 144 AN: 44432

Ashkenazi Jewish (ASJ) AF: 0.00715 AC: 185 AN: 25866

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.00342 AC: 290 AN: 84768

European-Finnish (FIN) AF: 0.000526 AC: 28 AN: 53248

Middle Eastern (MID) AF: 0.0262 AC: 151 AN: 5754

European-Non Finnish (NFE) AF: 0.00434 AC: 4812 AN: 1108444

Other (OTH) AF: 0.00483 AC: 291 AN: 60188

GnomAD4 genome AF: 0.00378 AC: 575 AN: 152314 Hom.: 4 Cov.: 33 AF XY: 0.00334 AC XY: 249 AN XY: 74468

African (AFR) AF: 0.000794 AC: 33 AN: 41566

American (AMR) AF: 0.00451 AC: 69 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4830

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10612

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00517 AC: 352 AN: 68028

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00513 Hom.: 8

Bravo AF: 0.00417

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00523 AC: 45

ExAC AF: 0.00402 AC: 488

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.0
DANN	Benign	0.61
DEOGEN2	Benign	0.065	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.040	N
PhyloP100		-0.029
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.55	N
REVEL	Benign	0.038
Sift	Benign	0.84	T
Sift4G	Benign	0.55	T
Polyphen		0.0010	B
Vest4		0.31
MVP		0.32
MPC		0.093
ClinPred		0.00087	T
GERP RS		1.4
Varity_R		0.023
gMVP		0.17
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs140893531; hg19: chr2-120209633; COSMIC: COSV50028070;