Genetic Variant SCTR:p.Ala213Ala (chr2-119461998-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PP3_ModerateBP6_ModerateBS2

The NM_002980.3(SCTR):c.639G>A(p.Ala213Ala) 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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0410

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 2-119461998-C-T is Benign according to our data. Variant chr2-119461998-C-T is described in ClinVar as Benign. ClinVar VariationId is 717175.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 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.639G>A	p.Ala213Ala	splice_region synonymous	Exon 7 of 13	NP_002971.2	P47872

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCTR	ENST00000019103.8	TSL:1 MANE Select	c.639G>A	p.Ala213Ala	splice_region synonymous	Exon 7 of 13	ENSP00000019103.6	P47872
SCTR	ENST00000903274.1		c.834G>A	p.Ala278Ala	splice_region synonymous	Exon 9 of 15	ENSP00000573333.1
SCTR	ENST00000903275.1		c.639G>A	p.Ala213Ala	splice_region synonymous	Exon 7 of 13	ENSP00000573334.1

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.000642

AC:

154

AN:

239748

AF XY:

0.000571

show subpopulations

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 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.:

Cov.:

AF XY:

0.000188

AC XY:

135

AN XY:

718946

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32856

American (AMR)

AF:

0.00528

AC:

228

AN:

43148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25598

East Asian (EAS)

AF:

0.00

AC:

AN:

38860

South Asian (SAS)

AF:

0.0000598

AC:

AN:

83602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5666

European-Non Finnish (NFE)

AF:

0.0000181

AC:

AN:

1103980

Other (OTH)

AF:

0.000503

AC:

AN:

59678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000296

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41556

American (AMR)

AF:

0.00242

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68016

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000131

Hom.:

Bravo

AF:

0.000506

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

0.041

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over