1-15462750-G-T

Variant names:

• chr1-15462750-G-T
• rs867241766
• NM_033440.3:c.245G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_033440.3(CELA2A):​c.245G>T​(p.Arg82Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R82H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CELA2A NM_033440.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.878

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELA2A	NM_033440.3	c.245G>T	p.Arg82Leu	missense_variant	Exon 4 of 8	ENST00000359621.5	NP_254275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELA2A	ENST00000359621.5	c.245G>T	p.Arg82Leu	missense_variant	Exon 4 of 8	1	NM_033440.3	ENSP00000352639.4
CELA2A	ENST00000459653.1	n.271G>T		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D
Eigen	Benign	0.12
Eigen_PC	Benign	0.055
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Benign	0.83	L
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.62
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.058	T
Polyphen		0.98	D
Vest4		0.59
MutPred		0.66		Loss of methylation at R82 (P = 0.0154);
MVP		0.79
MPC		0.44
ClinPred		0.75	D
GERP RS		3.2
Varity_R		0.43
gMVP		0.80

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

Other links and lift over

dbSNP: rs867241766; hg19: chr1-15789245;