chr7-130276673-G-A

Variant names:

• chr7-130276673-G-A
• rs376775678
• NM_001869.3:c.631G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001869.3(CPA2):​c.631G>A​(p.Asp211Asn) 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 benign outcome for this variant. 16/22 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. D211Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPA2 NM_001869.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.081804276).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001869.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA2	NM_001869.3	MANE Select	c.631G>A	p.Asp211Asn	missense	Exon 7 of 11	NP_001860.2	P48052

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA2	ENST00000222481.9	TSL:1 MANE Select	c.631G>A	p.Asp211Asn	missense	Exon 7 of 11	ENSP00000222481.4	P48052
	CPA2	ENST00000416698.1	TSL:5	n.*182G>A		non_coding_transcript_exon	Exon 8 of 8	ENSP00000395582.1	J3QT58
	CPA2	ENST00000487259.5	TSL:2	n.646G>A		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Benign	0.50
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.13	N
PhyloP100		0.38
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.084
Sift	Benign	0.67	T
Sift4G	Benign	0.86	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.53		Loss of helix (P = 0.1299)
MVP		0.17
MPC		0.11
ClinPred		0.065	T
GERP RS		3.9
Varity_R		0.093
gMVP		0.51
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs376775678; hg19: chr7-129916513;