Genetic Variant CTRB2:p.Val85Met (chr16-75205804-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001025200.4(CTRB2):c.253G>A(p.Val85Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 10)

Exomes 𝑓: 0.000024 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CTRB2
NM_001025200.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.477

Variant links:

Genes affected

CTRB2 (HGNC:2522): (chymotrypsinogen B2) This gene encodes a member of the serine protease family of enzymes and forms a principal precursor of the pancreatic proteolytic enzymes. The encoded preproprotein is synthesized in the acinar cells of the pancreas and secreted into the small intestine where it undergoes proteolytic activation to generate a functional enzyme. This CTRB2 gene is located head-to-head with the related CTRB1 gene. Some human populations have an alternate haplotype which inverts a 16.6 Kb region containing portions of intron 1, exon 1, and the upstream sequence of the CTRB1 and CTRB2 genes. In this inversion haplotype exon 1 and flanking sequence is swapped in CTRB1 and CTRB2. This inversion is associated with differential gene expression and increased risk for chronic pancreatitis. The GRCh38 assembly represents the minor allele for SNP rs8048956 of the CTRB1 gene. SNP rs8048956 is diagnostic for this inversion. [provided by RefSeq, Jan 2021]

CTRB2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTRB2	NM_001025200.4 link	c.253G>A	p.Val85Met	missense_variant	Exon 4 of 7	ENST00000303037.13	NP_001020371.3	Q6GPI1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTRB2	ENST00000303037.13 link	c.253G>A	p.Val85Met	missense_variant	Exon 4 of 7	1	NM_001025200.4	ENSP00000303963.8		Q6GPI1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

82100

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000870

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000308

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000585

AC:

AN:

85440

Hom.:

AF XY:

0.0000684

AC XY:

AN XY:

43848

show subpopulations

Gnomad AFR exome

AF:

0.000518

Gnomad AMR exome

AF:

0.0000651

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000305

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000235

AC:

AN:

764612

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

391926

show subpopulations

Gnomad4 AFR exome

AF:

0.000490

Gnomad4 AMR exome

AF:

0.0000323

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000171

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000133

Gnomad4 OTH exome

AF:

0.0000277

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000207

AC:

AN:

82138

Hom.:

Cov.:

AF XY:

0.000133

AC XY:

AN XY:

37684

show subpopulations

Gnomad4 AFR

AF:

0.000929

Gnomad4 AMR

AF:

0.000111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000309

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000297

Hom.:

ExAC

AF:

0.0000531

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.253G>A (p.V85M) alteration is located in exon 4 (coding exon 4) of the CTRB2 gene. This alteration results from a G to A substitution at nucleotide position 253, causing the valine (V) at amino acid position 85 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.77

D;.;.

Eigen

Benign

0.022

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.85

D;D;D

M_CAP

Pathogenic

0.30

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Uncertain

0.35

MutationAssessor

Uncertain

2.2

M;.;.

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.5

D;D;N

REVEL

Uncertain

0.54

Sift

Uncertain

0.024

D;T;D

Sift4G

Uncertain

0.020

D;D;D

Polyphen

0.99

D;.;.

Vest4

0.14

MutPred

0.58

Gain of disorder (P = 0.1171);.;.;

MVP

0.91

MPC

0.38

ClinPred

0.11

GERP RS

3.4

Varity_R

0.24

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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