chr2-119461980-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002980.3(SCTR):​c.657G>T​(p.Met219Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000212 in 1,606,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SCTR
NM_002980.3 missense

Scores

2
5
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.70
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32632512).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCTRNM_002980.3 linkuse as main transcriptc.657G>T p.Met219Ile missense_variant 7/13 ENST00000019103.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCTRENST00000019103.8 linkuse as main transcriptc.657G>T p.Met219Ile missense_variant 7/131 NM_002980.3 P1
SCTRENST00000485440.1 linkuse as main transcriptn.1337G>T non_coding_transcript_exon_variant 4/102
SCTRENST00000627145.1 linkuse as main transcript downstream_gene_variant 5
SCTRENST00000630739.2 linkuse as main transcript downstream_gene_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000246
AC:
6
AN:
243938
Hom.:
0
AF XY:
0.0000379
AC XY:
5
AN XY:
131860
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000138
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000180
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000213
AC:
31
AN:
1454408
Hom.:
0
Cov.:
31
AF XY:
0.0000235
AC XY:
17
AN XY:
723298
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000106
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.0000333
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152188
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000247
AC:
3
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.70
BayesDel_addAF
Benign
-0.060
T
BayesDel_noAF
Uncertain
-0.070
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.22
T
Eigen
Benign
0.013
Eigen_PC
Benign
0.20
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.33
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.54
T
PROVEAN
Uncertain
-2.7
D
REVEL
Benign
0.18
Sift
Benign
0.094
T
Sift4G
Benign
0.13
T
Polyphen
0.12
B
Vest4
0.50
MutPred
0.52
Loss of catalytic residue at M219 (P = 0.0057);
MVP
0.60
MPC
0.41
ClinPred
0.79
D
GERP RS
5.1
Varity_R
0.61
gMVP
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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.

Other links and lift over

dbSNP: rs199636057; hg19: chr2-120219556; API