NM_001869.3:c.619A>C

Variant names:

• chr7-130276661-A-C
• rs79082583
• NM_001869.3:c.619A>C

Variant summary

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

The NM_001869.3(CPA2):​c.619A>C​(p.Thr207Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPA2 NM_001869.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.05

Genes affected

CPA2 (HGNC:2297): (carboxypeptidase A2) Three different forms of human pancreatic procarboxypeptidase A have been isolated. The encoded protein represents the A2 form, which is a monomeric protein with different biochemical properties from the A1 and A3 forms. The A2 form of pancreatic procarboxypeptidase acts on aromatic C-terminal residues and is a secreted protein. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPA2	NM_001869.3	c.619A>C	p.Thr207Pro	missense_variant	Exon 7 of 11	ENST00000222481.9	NP_001860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPA2	ENST00000222481.9	c.619A>C	p.Thr207Pro	missense_variant	Exon 7 of 11	1	NM_001869.3	ENSP00000222481.4
CPA2	ENST00000416698.1	n.*170A>C		non_coding_transcript_exon_variant	Exon 8 of 8	5		ENSP00000395582.1
CPA2	ENST00000487259.5	n.634A>C		non_coding_transcript_exon_variant	Exon 7 of 7	2
CPA2	ENST00000416698.1	n.*170A>C		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000395582.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.022	D
Polyphen		0.19	B
Vest4		0.55
MutPred		0.62		Gain of disorder (P = 0.0619);
MVP		0.53
MPC		0.61
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.96
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs79082583; hg19: chr7-129916501;