chr7-130276673-G-C

Variant names:

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

Variant summary

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

The NM_001869.3(CPA2):​c.631G>C​(p.Asp211His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,070 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CPA2 NM_001869.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378

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.631G>C	p.Asp211His	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.631G>C	p.Asp211His	missense_variant	Exon 7 of 11	1	NM_001869.3	ENSP00000222481.4
CPA2	ENST00000416698.1	n.*182G>C		non_coding_transcript_exon_variant	Exon 8 of 8	5		ENSP00000395582.1
CPA2	ENST00000487259.5	n.646G>C		non_coding_transcript_exon_variant	Exon 7 of 7	2
CPA2	ENST00000416698.1	n.*182G>C		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000395582.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251358 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135854

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460070 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 726492

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.86	P
Vest4		0.33
MutPred		0.56		Loss of catalytic residue at D211 (P = 0.0247);
MVP		0.54
MPC		0.14
ClinPred		0.91	D
GERP RS		3.9
Varity_R		0.33
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs376775678; hg19: chr7-129916513;