chr1-15461588-A-C

Variant summary

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

The NM_033440.3(CELA2A):ā€‹c.157A>Cā€‹(p.Lys53Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000225 in 1,612,408 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.00016 ( 0 hom., cov: 33)
Exomes š‘“: 0.00023 ( 2 hom. )

Consequence

CELA2A
NM_033440.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.67
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]

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=0.024432361).
BP6
Variant 1-15461588-A-C is Benign according to our data. Variant chr1-15461588-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2207009.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CELA2ANM_033440.3 linkuse as main transcriptc.157A>C p.Lys53Gln missense_variant 3/8 ENST00000359621.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CELA2AENST00000359621.5 linkuse as main transcriptc.157A>C p.Lys53Gln missense_variant 3/81 NM_033440.3 P1
CELA2AENST00000459653.1 linkuse as main transcriptn.183A>C non_coding_transcript_exon_variant 3/42

Frequencies

GnomAD3 genomes
AF:
0.000158
AC:
24
AN:
152194
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000620
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000231
AC:
58
AN:
251388
Hom.:
1
AF XY:
0.000258
AC XY:
35
AN XY:
135866
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000231
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000653
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000238
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000231
AC:
338
AN:
1460096
Hom.:
2
Cov.:
31
AF XY:
0.000248
AC XY:
180
AN XY:
726360
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.000638
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000221
Gnomad4 OTH exome
AF:
0.000216
GnomAD4 genome
AF:
0.000158
AC:
24
AN:
152312
Hom.:
0
Cov.:
33
AF XY:
0.000161
AC XY:
12
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000254
Hom.:
0
Bravo
AF:
0.000147
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.000272
AC:
33
EpiCase
AF:
0.000218
EpiControl
AF:
0.000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsSep 29, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
0.0020
DANN
Benign
0.42
DEOGEN2
Benign
0.20
T
Eigen
Benign
-2.2
Eigen_PC
Benign
-2.3
FATHMM_MKL
Benign
0.0087
N
LIST_S2
Benign
0.093
T
M_CAP
Benign
0.047
D
MetaRNN
Benign
0.024
T
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
0.13
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.19
N
REVEL
Benign
0.29
Sift
Benign
0.21
T
Sift4G
Benign
0.51
T
Polyphen
0.0010
B
Vest4
0.26
MVP
0.17
MPC
0.34
ClinPred
0.11
T
GERP RS
-8.6
Varity_R
0.056
gMVP
0.35

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.

Other links and lift over

dbSNP: rs150024502; hg19: chr1-15788083; COSMIC: COSV62747590; COSMIC: COSV62747590; API