NM_014255.7:c.375C>T

Variant names:

• chr12-56311244-G-A
• rs76871886
• NM_014255.7:c.375C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_014255.7(CNPY2):​c.375C>T​(p.Ile125Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,614,104 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (13 hom.)
• Consequence: CNPY2 NM_014255.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.194
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 12-56311244-G-A is Benign according to our data. Variant chr12-56311244-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2643090.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.194 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 13 AR gene

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.375C>T	p.Ile125Ile	synonymous	Exon 4 of 6	NP_055070.1	Q9Y2B0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNPY2	ENST00000273308.9	TSL:1 MANE Select	c.375C>T	p.Ile125Ile	synonymous	Exon 4 of 6	ENSP00000273308.4	Q9Y2B0-1
	ENSG00000144785	ENST00000549318.5	TSL:5	c.375C>T	p.Ile125Ile	synonymous	Exon 4 of 9	ENSP00000446743.1	F8W031
	CNPY2	ENST00000929942.1		c.375C>T	p.Ile125Ile	synonymous	Exon 4 of 6	ENSP00000600001.1

Frequencies

GnomAD3 genomes AF: 0.00183 AC: 278 AN: 152144 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00304

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00208 AC: 524 AN: 251380 AF XY: 0.00190

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00407

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00259

Gnomad NFE exome AF: 0.00333

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00288 AC: 4212 AN: 1461842 Hom.: 13 Cov.: 31 AF XY: 0.00282 AC XY: 2053 AN XY: 727212

African (AFR) AF: 0.000448 AC: 15 AN: 33480

American (AMR) AF: 0.000760 AC: 34 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00421 AC: 110 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86252

European-Finnish (FIN) AF: 0.00271 AC: 145 AN: 53418

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00336 AC: 3736 AN: 1111978

Other (OTH) AF: 0.00263 AC: 159 AN: 60386

GnomAD4 genome AF: 0.00183 AC: 278 AN: 152262 Hom.: 1 Cov.: 32 AF XY: 0.00165 AC XY: 123 AN XY: 74446

African (AFR) AF: 0.000433 AC: 18 AN: 41556

American (AMR) AF: 0.000458 AC: 7 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00304 AC: 207 AN: 68020

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00230 Hom.: 2

Bravo AF: 0.00170

EpiCase AF: 0.00262

EpiControl AF: 0.00279

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	11
DANN	Benign	0.91
PhyloP100		0.19
Mutation Taster		=98/2	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

Other links and lift over

dbSNP: rs76871886; hg19: chr12-56705028; COSMIC: COSV99836426; COSMIC: COSV99836426;