Variant 12-56314961-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014255.7(CNPY2):c.94A>G(p.Arg32Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,976 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 1 hom. )

Consequence

CNPY2
NM_014255.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12

Variant links:

Genes affected

CNPY2 (HGNC:13529): (canopy FGF signaling regulator 2) Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

CNPY2 links:

ENSG00000144785 (HGNC:):

ENSG00000144785 links:

CNPY2-AS1 (HGNC:55480): (CNPY2 antisense RNA 1)

CNPY2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.15358666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNPY2	NM_014255.7 link	c.94A>G	p.Arg32Gly	missense_variant	3/6	ENST00000273308.9	NP_055070.1
CNPY2	NM_001190991.3 link	c.94A>G	p.Arg32Gly	missense_variant	3/3		NP_001177920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNPY2	ENST00000273308.9 link	c.94A>G	p.Arg32Gly	missense_variant	3/6	1	NM_014255.7	ENSP00000273308.4		Q9Y2B0-1
ENSG00000144785	ENST00000549318.5 link	c.94A>G	p.Arg32Gly	missense_variant	3/9	5		ENSP00000446743.1		F8W031

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000155

AC:

AN:

251460

Hom.:

AF XY:

0.0000957

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00113

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:

0.0000274

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000872

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:

0.0000166

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000831

Hom.:

Bravo

AF:

0.000204

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2024

The c.94A>G (p.R32G) alteration is located in exon 3 (coding exon 2) of the CNPY2 gene. This alteration results from a A to G substitution at nucleotide position 94, causing the arginine (R) at amino acid position 32 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

.;.;.;T;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.93

D;D;D;D;D

M_CAP

Benign

0.070

MetaRNN

Benign

0.15

T;T;T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Pathogenic

3.0

.;.;.;M;.

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.8

D;D;D;D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0060

D;D;D;D;D

Sift4G

Uncertain

0.0070

D;.;.;D;.

Polyphen

1.0

.;.;.;D;.

Vest4

0.89

MutPred

0.44

Gain of catalytic residue at C31 (P = 0.003);Gain of catalytic residue at C31 (P = 0.003);Gain of catalytic residue at C31 (P = 0.003);Gain of catalytic residue at C31 (P = 0.003);Gain of catalytic residue at C31 (P = 0.003);

MVP

0.62

MPC

1.5

ClinPred

0.47

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.47

gMVP

0.99

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