Genetic Variant CELA2A:p.Asn257Ser (chr1-15467516-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_033440.3(CELA2A):c.770A>G(p.Asn257Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00552 in 1,614,118 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0040 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0057 ( 38 hom. )

Consequence

CELA2A
NM_033440.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.86

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025982976).

BS2

High AC in GnomAd4 at 613 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELA2A	NM_033440.3 link	c.770A>G	p.Asn257Ser	missense_variant	Exon 7 of 8	ENST00000359621.5	NP_254275.1	P08217
LOC105376767	XR_002958256.2 link	n.-11T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELA2A	ENST00000359621.5 link	c.770A>G	p.Asn257Ser	missense_variant	Exon 7 of 8	1	NM_033440.3	ENSP00000352639.4		P08217
CELA2B	ENST00000494280.1 link	n.367A>G		non_coding_transcript_exon_variant	Exon 2 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.00403

AC:

613

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00667

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00408

AC:

1027

AN:

251408

Hom.:

AF XY:

0.00446

AC XY:

606

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00578

Gnomad FIN exome

AF:

0.00291

Gnomad NFE exome

AF:

0.00580

Gnomad OTH exome

AF:

0.00441

GnomAD4 exome

AF:

0.00567

AC:

8290

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00575

AC XY:

4185

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000836

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.00329

Gnomad4 EAS exome

AF:

0.00169

Gnomad4 SAS exome

AF:

0.00635

Gnomad4 FIN exome

AF:

0.00206

Gnomad4 NFE exome

AF:

0.00632

Gnomad4 OTH exome

AF:

0.00474

GnomAD4 genome

AF:

0.00403

AC:

613

AN:

152274

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

295

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.00519

Gnomad4 FIN

AF:

0.00349

Gnomad4 NFE

AF:

0.00667

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00544

Hom.:

Bravo

AF:

0.00352

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00640

AC:

ExAC

AF:

0.00427

AC:

518

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00600

EpiControl

AF:

0.00676

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

4.6

DANN

Benign

0.62

DEOGEN2

Benign

0.16

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.20

M_CAP

Benign

0.0098

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.72

MutationAssessor

Benign

-0.21

PrimateAI

Benign

0.30

PROVEAN

Benign

0.48

REVEL

Benign

0.17

Sift

Benign

0.14

Sift4G

Benign

0.22

Polyphen

0.0030

Vest4

0.10

MVP

0.38

MPC

0.26

ClinPred

0.0029

GERP RS

1.9

Varity_R

0.038

gMVP

0.39

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over