2-219172848-G-A

Variant names:

• chr2-219172848-G-A
• rs144214406
• NM_015680.6:c.971C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015680.6(CNPPD1):​c.971C>T​(p.Pro324Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. P324R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNPPD1 NM_015680.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21
• Publications: 0 publications found

Genes affected

CNPPD1 (HGNC:25220): (cyclin Pas1/PHO80 domain containing 1) Predicted to enable cyclin-dependent protein serine/threonine kinase regulator activity. Predicted to be involved in regulation of cyclin-dependent protein serine/threonine kinase activity. Predicted to be integral component of membrane. Predicted to be part of cyclin-dependent protein kinase holoenzyme complex. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.08609095).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015680.6. 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
	CNPPD1	NM_015680.6	MANE Select	c.971C>T	p.Pro324Leu	missense	Exon 8 of 8	NP_056495.4
	CNPPD1	NM_001321389.2		c.971C>T	p.Pro324Leu	missense	Exon 9 of 9	NP_001308318.2	Q9BV87
	CNPPD1	NM_001321390.2		c.971C>T	p.Pro324Leu	missense	Exon 9 of 9	NP_001308319.2	Q9BV87

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNPPD1	ENST00000360507.10	TSL:1 MANE Select	c.971C>T	p.Pro324Leu	missense	Exon 8 of 8	ENSP00000353698.5	Q9BV87
	CNPPD1	ENST00000409789.5	TSL:1	c.971C>T	p.Pro324Leu	missense	Exon 9 of 9	ENSP00000386277.1	Q9BV87
	CNPPD1	ENST00000874465.1		c.1052C>T	p.Pro351Leu	missense	Exon 8 of 8	ENSP00000544524.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-0.049
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.2
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.043
Sift	Benign	0.052	T
Sift4G	Benign	0.13	T
Polyphen		0.44	B
Vest4		0.26
MutPred		0.18		Loss of glycosylation at P324 (P = 0.0045)
MVP		0.25
MPC		0.78
ClinPred		0.78	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.041
gMVP		0.28
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144214406; hg19: chr2-220037570;