1-15466073-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_033440.3(CELA2A):c.568G>A(p.Ala190Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000453 in 1,614,132 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 2 hom. )

Consequence

CELA2A
NM_033440.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0700

Publications

2 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 links:

CELA2B (HGNC:29995): (chymotrypsin like elastase 2B) 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 2B is secreted from the pancreas as a zymogen. In other species, elastase 2B has been shown to preferentially cleave proteins after leucine, methionine, and phenylalanine residues. [provided by RefSeq, Jul 2008]

CELA2B links:

LOC105376767 (HGNC:):

LOC105376767 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.049302876).

BS2

High AC in GnomAd4 at 49 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.568G>A	p.Ala190Thr	missense	Exon 6 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.568G>A	p.Ala190Thr	missense	Exon 6 of 8	ENSP00000352639.4	P08217
CELA2A	ENST00000967096.1		c.439G>A	p.Ala147Thr	missense	Exon 5 of 7	ENSP00000637155.1
CELA2B	ENST00000494280.1	TSL:5	n.165G>A		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000647

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000314

AC:

AN:

251476

AF XY:

0.000368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000589

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000467

AC:

682

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000448

AC XY:

326

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.000112

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000336

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000562

AC:

625

AN:

1111996

Other (OTH)

AF:

0.000348

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

126

168

210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<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:

0.000322

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

41546

American (AMR)

AF:

0.0000654

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000647

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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:

0.000583

Hom.:

Bravo

AF:

0.000366

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000313

AC:

EpiCase

AF:

0.000818

EpiControl

AF:

0.000889

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.41

CADD

Benign

4.6

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.78

M_CAP

Benign

0.015

MetaRNN

Benign

0.049

MetaSVM

Benign

-0.66

MutationAssessor

Benign

0.33

PhyloP100

-0.070

PrimateAI

Benign

0.31

PROVEAN

Benign

0.38

REVEL

Benign

0.15

Sift

Benign

0.075

Sift4G

Benign

0.074

Polyphen

0.0010

Vest4

0.14

MVP

0.38

MPC

0.31

ClinPred

0.035

GERP RS

-1.3

Varity_R

0.026

gMVP

0.41

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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