chr1-15467497-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_033440.3(CELA2A):​c.751G>A​(p.Val251Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

CELA2A
NM_033440.3 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.66
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BS2
High AC in GnomAd4 at 8 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.751G>A p.Val251Ile missense_variant 7/8 ENST00000359621.5
LOC105376767XR_002958256.2 linkuse as main transcriptn.9C>T non_coding_transcript_exon_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CELA2AENST00000359621.5 linkuse as main transcriptc.751G>A p.Val251Ile missense_variant 7/81 NM_033440.3 P1
CELA2BENST00000494280.1 linkuse as main transcriptn.348G>A non_coding_transcript_exon_variant 2/65

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152186
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000955
AC:
24
AN:
251432
Hom.:
0
AF XY:
0.0000662
AC XY:
9
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000879
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000105
AC:
154
AN:
1461848
Hom.:
0
Cov.:
33
AF XY:
0.0000990
AC XY:
72
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.000268
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000109
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152186
Hom.:
0
Cov.:
31
AF XY:
0.0000942
AC XY:
7
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000115
Hom.:
0
Bravo
AF:
0.000117
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000107
AC:
13
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 GeneticsDec 20, 2023The c.751G>A (p.V251I) alteration is located in exon 7 (coding exon 7) of the CELA2A gene. This alteration results from a G to A substitution at nucleotide position 751, causing the valine (V) at amino acid position 251 to be replaced by an isoleucine (I). 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
Benign
0.19
BayesDel_addAF
Benign
-0.097
T
BayesDel_noAF
Uncertain
-0.080
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.27
T
Eigen
Benign
0.027
Eigen_PC
Benign
0.022
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.64
T
M_CAP
Benign
0.018
T
MetaRNN
Uncertain
0.63
D
MetaSVM
Uncertain
0.20
D
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
0.99
D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-0.81
N
REVEL
Uncertain
0.53
Sift
Benign
0.046
D
Sift4G
Uncertain
0.047
D
Polyphen
0.58
P
Vest4
0.65
MVP
0.68
MPC
0.33
ClinPred
0.20
T
GERP RS
3.1
Varity_R
0.17
gMVP
0.51

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: rs376888050; hg19: chr1-15793992; COSMIC: COSV62747244; COSMIC: COSV62747244; API