1-15466127-G-C

Variant names:

• chr1-15466127-G-C
• NM_033440.3:c.622G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033440.3(CELA2A):​c.622G>C​(p.Val208Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. V208M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CELA2A NM_033440.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298

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]

LOC105376767 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09142697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELA2A	NM_033440.3	c.622G>C	p.Val208Leu	missense_variant	Exon 6 of 8	ENST00000359621.5	NP_254275.1
LOC105376767	XR_002958256.2	n.366+1013C>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELA2A	ENST00000359621.5	c.622G>C	p.Val208Leu	missense_variant	Exon 6 of 8	1	NM_033440.3	ENSP00000352639.4
CELA2B	ENST00000494280.1	n.219G>C		non_coding_transcript_exon_variant	Exon 1 of 6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461680 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727120

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.32	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.065	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.23	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.16
Sift	Benign	0.10	T
Sift4G	Benign	0.18	T
Polyphen		0.037	B
Vest4		0.18
MutPred		0.49		Gain of disorder (P = 0.2229);
MVP		0.33
MPC		0.32
ClinPred		0.12	T
GERP RS		0.38
Varity_R		0.23
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-15792622;