Variant 1-15462809-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_033440.3(CELA2A):c.304G>T(p.Val102Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,614,088 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 30 hom. )

Consequence

CELA2A
NM_033440.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.50

Variant links:

Genes affected

CELA2A (HGNC:24609): (chymotrypsin like elastase 2A) Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin. Humans have six elastase genes which encode the structurally similar proteins elastase 1, 2, 2A, 2B, 3A, and 3B. Like most of the human elastases, elastase 2A is secreted from the pancreas as a zymogen. In other species, elastase 2A has been shown to preferentially cleave proteins after leucine, methionine, and phenylalanine residues. [provided by RefSeq, May 2009]

CELA2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014178455).

BP6

Variant 1-15462809-G-T is Benign according to our data. Variant chr1-15462809-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3257603.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-15462809-G-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 296 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELA2A	NM_033440.3 linkuse as main transcript	c.304G>T	p.Val102Phe	missense_variant	4/8	ENST00000359621.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELA2A	ENST00000359621.5 linkuse as main transcript	c.304G>T	p.Val102Phe	missense_variant	4/8	1	NM_033440.3	P1
CELA2A	ENST00000459653.1 linkuse as main transcript	n.330G>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.00195

AC:

297

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.00705

Gnomad FIN

AF:

0.0153

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00330

AC:

829

AN:

251472

Hom.:

AF XY:

0.00360

AC XY:

489

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00359

Gnomad SAS exome

AF:

0.00774

Gnomad FIN exome

AF:

0.0160

Gnomad NFE exome

AF:

0.00131

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00162

AC:

2367

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1326

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00403

Gnomad4 SAS exome

AF:

0.00784

Gnomad4 FIN exome

AF:

0.0160

Gnomad4 NFE exome

AF:

0.000468

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

AF:

0.00194

AC:

296

AN:

152218

Hom.:

Cov.:

AF XY:

0.00257

AC XY:

191

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00405

Gnomad4 SAS

AF:

0.00685

Gnomad4 FIN

AF:

0.0153

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000870

Hom.:

Bravo

AF:

0.000468

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00359

AC:

436

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

CELA2A: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Pathogenic

0.17

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.72

Eigen

Benign

0.11

Eigen_PC

Benign

-0.086

FATHMM_MKL

Benign

0.49

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.014

MetaSVM

Pathogenic

0.90

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

0.90

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.7

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.024

Polyphen

0.99

Vest4

0.62

MVP

0.79

MPC

1.2

ClinPred

0.074

GERP RS

4.1

Varity_R

0.76

gMVP

0.82

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