Genetic Variant CNPY2:p.Thr17Ile (chr12-56315168-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014255.7(CNPY2):c.50C>T(p.Thr17Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. T17S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CNPY2
NM_014255.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.910

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

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=0.09422174).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014255.7. 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
	CNPY2	NM_014255.7	MANE Select	c.50C>T	p.Thr17Ile	missense	Exon 2 of 6	NP_055070.1	Q9Y2B0-1
	CNPY2	NM_001190991.3		c.50C>T	p.Thr17Ile	missense	Exon 2 of 3	NP_001177920.1	Q9Y2B0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNPY2	ENST00000273308.9	TSL:1 MANE Select	c.50C>T	p.Thr17Ile	missense	Exon 2 of 6	ENSP00000273308.4	Q9Y2B0-1
ENSG00000144785	ENST00000549318.5	TSL:5	c.50C>T	p.Thr17Ile	missense	Exon 2 of 9	ENSP00000446743.1	F8W031
CNPY2	ENST00000546388.1	TSL:1	n.152C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251382

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461748

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727174

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111934

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.033

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.68

M_CAP

Benign

0.0028

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.77

PhyloP100

0.91

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.92

REVEL

Benign

0.058

Sift

Benign

0.26

Sift4G

Benign

0.26

Polyphen

0.0

Vest4

0.43

MutPred

0.40

Gain of catalytic residue at A18 (P = 2e-04)

MVP

0.10

MPC

0.49

ClinPred

0.22

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.049

gMVP

0.66

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over