chr1-15457149-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS2_Supporting

The NM_033440.3(CELA2A):​c.104C>T​(p.Ala35Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,614,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

CELA2A
NM_033440.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0700
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 Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.053507835).
BS2
High AC in GnomAd4 at 7 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CELA2ANM_033440.3 linkuse as main transcriptc.104C>T p.Ala35Val missense_variant 2/8 ENST00000359621.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CELA2AENST00000359621.5 linkuse as main transcriptc.104C>T p.Ala35Val missense_variant 2/81 NM_033440.3 P1
CELA2AENST00000459653.1 linkuse as main transcriptn.130C>T non_coding_transcript_exon_variant 2/42
CELA2AENST00000497590.1 linkuse as main transcriptn.111C>T non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152158
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000769
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000517
AC:
13
AN:
251420
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000381
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000253
AC:
37
AN:
1461878
Hom.:
0
Cov.:
31
AF XY:
0.0000220
AC XY:
16
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000252
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152276
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000771
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.0000494
AC:
6
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 18, 2023The c.104C>T (p.A35V) alteration is located in exon 2 (coding exon 2) of the CELA2A gene. This alteration results from a C to T substitution at nucleotide position 104, causing the alanine (A) at amino acid position 35 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
5.5
DANN
Uncertain
0.99
DEOGEN2
Benign
0.37
T
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.032
N
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.054
T
MetaSVM
Uncertain
-0.24
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-1.8
N
REVEL
Uncertain
0.30
Sift
Benign
0.18
T
Sift4G
Benign
0.16
T
Polyphen
0.75
P
Vest4
0.15
MVP
0.55
MPC
0.35
ClinPred
0.054
T
GERP RS
-1.7
Varity_R
0.057
gMVP
0.64

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: rs147042451; hg19: chr1-15783644; API