Genetic Variant CELA2A:c.494-68C>G (chr1-15465931-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033440.3(CELA2A):c.494-68C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,569,754 control chromosomes in the GnomAD database, including 45,287 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 11165 hom., cov: 31)

Exomes 𝑓: 0.20 ( 34122 hom. )

Consequence

CELA2A
NM_033440.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.74

Publications

18 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELA2A	NM_033440.3 link	c.494-68C>G		intron_variant	Intron 5 of 7	ENST00000359621.5	NP_254275.1	P08217
LOC105376767	XR_002958256.2 link	n.367-1059G>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELA2A	ENST00000359621.5 link	c.494-68C>G		intron_variant	Intron 5 of 7	1	NM_033440.3	ENSP00000352639.4		P08217
CELA2B	ENST00000494280.1 link	n.23C>G		non_coding_transcript_exon_variant	Exon 1 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48950

AN:

151904

Hom.:

11136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.647

Gnomad AMI

AF:

0.178

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.0765

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.312

GnomAD4 exome

AF:

0.205

AC:

290259

AN:

1417732

Hom.:

34122

Cov.:

AF XY:

0.204

AC XY:

144363

AN XY:

706034

show subpopulations

African (AFR)

AF:

0.652

AC:

21197

AN:

32492

American (AMR)

AF:

0.140

AC:

6176

AN:

44204

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

6185

AN:

25246

East Asian (EAS)

AF:

0.0872

AC:

3435

AN:

39372

South Asian (SAS)

AF:

0.208

AC:

17585

AN:

84512

European-Finnish (FIN)

AF:

0.207

AC:

10841

AN:

52402

Middle Eastern (MID)

AF:

0.268

AC:

1206

AN:

4498

European-Non Finnish (NFE)

AF:

0.196

AC:

210456

AN:

1076182

Other (OTH)

AF:

0.224

AC:

13178

AN:

58824

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

11007

22014

33021

44028

55035

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7270

14540

21810

29080

36350

<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:

0.322

AC:

49027

AN:

152022

Hom.:

11165

Cov.:

AF XY:

0.317

AC XY:

23527

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.647

AC:

26830

AN:

41444

American (AMR)

AF:

0.210

AC:

3207

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

808

AN:

3470

East Asian (EAS)

AF:

0.0768

AC:

398

AN:

5180

South Asian (SAS)

AF:

0.183

AC:

881

AN:

4820

European-Finnish (FIN)

AF:

0.211

AC:

2228

AN:

10548

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.203

AC:

13776

AN:

67982

Other (OTH)

AF:

0.310

AC:

653

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1382

2764

4147

5529

6911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

432

864

1296

1728

2160

<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:

0.193

Hom.:

1777

Bravo

AF:

0.339

Asia WGS

AF:

0.186

AC:

644

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.83

(source)

DANN

Benign

0.39

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over