Genetic Variant NM_033440.3:c.304G>T (chr1-15462809-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

abdominal obesity-metabolic syndrome 4
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

CELA2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3257603.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 296 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033440.3. 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
	CELA2A	NM_033440.3	MANE Select	c.304G>T	p.Val102Phe	missense	Exon 4 of 8	NP_254275.1	P08217

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CELA2A	ENST00000359621.5	TSL:1 MANE Select	c.304G>T	p.Val102Phe	missense	Exon 4 of 8	ENSP00000352639.4	P08217
CELA2A	ENST00000967096.1		c.228-577G>T		intron	N/A	ENSP00000637155.1
CELA2A	ENST00000459653.1	TSL:2	n.330G>T		non_coding_transcript_exon	Exon 4 of 4

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

GnomAD2 exomes

AF:

0.00330

AC:

829

AN:

251472

AF XY:

0.00360

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 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

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.000179

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26136

East Asian (EAS)

AF:

0.00403

AC:

160

AN:

39698

South Asian (SAS)

AF:

0.00784

AC:

676

AN:

86256

European-Finnish (FIN)

AF:

0.0160

AC:

857

AN:

53408

Middle Eastern (MID)

AF:

0.00485

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000468

AC:

520

AN:

1112004

Other (OTH)

AF:

0.00189

AC:

114

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

134

268

402

536

670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00194

AC:

296

AN:

152218

Hom.:

Cov.:

AF XY:

0.00257

AC XY:

191

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41536

American (AMR)

AF:

0.000196

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00405

AC:

AN:

5182

South Asian (SAS)

AF:

0.00685

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0153

AC:

162

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00103

AC:

AN:

68020

Other (OTH)

AF:

0.00190

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00102

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

ClinVar submissions

Significance:Likely 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

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Pathogenic

0.17

CADD

Benign

(source)

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

PhyloP100

2.5

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

Mutation Taster

=93/7

polymorphism

(source)

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

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