7-130269714-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001869.3(CPA2):c.199G>A(p.Val67Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,614,124 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 45 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 36 hom. )

Consequence

CPA2
NM_001869.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.372

Variant links:

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]

CPA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041150153).

BP6

Variant 7-130269714-G-A is Benign according to our data. Variant chr7-130269714-G-A is described in ClinVar as [Benign]. Clinvar id is 783832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0124 (1884/152238) while in subpopulation AFR AF = 0.043 (1786/41528). AF 95% confidence interval is 0.0413. There are 45 homozygotes in GnomAd4. There are 903 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPA2	NM_001869.3 link	c.199G>A	p.Val67Ile	missense_variant	Exon 3 of 11	ENST00000222481.9	NP_001860.2	P48052

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CPA2	ENST00000222481.9 link	c.199G>A	p.Val67Ile	missense_variant	Exon 3 of 11	1	NM_001869.3	ENSP00000222481.4	P48052
CPA2	ENST00000416698.1 link	n.193G>A		non_coding_transcript_exon_variant	Exon 3 of 8	5		ENSP00000395582.1	J3QT58
CPA2	ENST00000480781.5 link	n.216G>A		non_coding_transcript_exon_variant	Exon 3 of 5	2
CPA2	ENST00000487259.5 link	n.214G>A		non_coding_transcript_exon_variant	Exon 3 of 7	2

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1886

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0431

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0119

GnomAD2 exomes

AF:

0.00297

AC:

746

AN:

251488

AF XY:

0.00232

show subpopulations

Gnomad AFR exome

AF:

0.0403

Gnomad AMR exome

AF:

0.00179

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00128

AC:

1867

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

880

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0456

AC:

1525

AN:

33478

Gnomad4 AMR exome

AF:

0.00206

AC:

AN:

44724

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.0000252

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.0000696

AC:

AN:

86258

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53420

Gnomad4 NFE exome

AF:

0.0000459

AC:

AN:

1112006

Gnomad4 Remaining exome

AF:

0.00273

AC:

165

AN:

60396

Heterozygous variant carriers

184

277

369

461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0124

AC:

1884

AN:

152238

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

903

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0430

AC:

0.0430071

AN:

0.0430071

Gnomad4 AMR

AF:

0.00399

AC:

0.00398745

AN:

0.00398745

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000162

AC:

0.000161717

AN:

0.000161717

Gnomad4 OTH

AF:

0.0118

AC:

0.0118147

AN:

0.0118147

Heterozygous variant carriers

184

275

367

459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00504

Hom.:

Bravo

AF:

0.0140

ESP6500AA

AF:

0.0345

AC:

152

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00358

AC:

435

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.019

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.27

REVEL

Benign

0.066

Sift

Benign

0.52

Sift4G

Benign

0.61

Polyphen

0.21

Vest4

0.079

MVP

0.14

MPC

0.20

ClinPred

0.0054

GERP RS

3.6

Varity_R

0.083

gMVP

0.29

Mutation Taster

=86/14

polymorphism

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over