NM_014255.7:c.194C>T

Variant names:

• chr12-56314861-G-A
• rs1873843456
• NM_014255.7:c.194C>T

Variant summary

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

The NM_014255.7(CNPY2):​c.194C>T​(p.Ser65Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNPY2 NM_014255.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.71
• Publications: 0 publications found

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]

ENSG00000144785 (HGNC:):

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.194C>T	p.Ser65Leu	missense	Exon 3 of 6	NP_055070.1	Q9Y2B0-1
	CNPY2	NM_001190991.3		c.194C>T	p.Ser65Leu	missense	Exon 3 of 3	NP_001177920.1	Q9Y2B0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNPY2	ENST00000273308.9	TSL:1 MANE Select	c.194C>T	p.Ser65Leu	missense	Exon 3 of 6	ENSP00000273308.4	Q9Y2B0-1
	ENSG00000144785	ENST00000549318.5	TSL:5	c.194C>T	p.Ser65Leu	missense	Exon 3 of 9	ENSP00000446743.1	F8W031
	CNPY2	ENST00000546388.1	TSL:1	n.459C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.7
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.22
Sift	Benign	0.21	T
Sift4G	Benign	0.11	T
Polyphen		0.91	P
Vest4		0.50
MutPred		0.27		Gain of catalytic residue at P60 (P = 0.001)
MVP		0.64
MPC		0.42
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.34
gMVP		0.81
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs1873843456; hg19: chr12-56708645;