2-219172701-A-T

Position:

• chr2-219172701-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015680.6(CNPPD1):​c.1118T>A​(p.Leu373Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,638 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CNPPD1 NM_015680.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33

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

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=0.10289267).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNPPD1	NM_015680.6	c.1118T>A	p.Leu373Gln	missense_variant	8/8	ENST00000360507.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNPPD1	ENST00000360507.10	c.1118T>A	p.Leu373Gln	missense_variant	8/8	1	NM_015680.6	P1
CNPPD1	ENST00000409789.5	c.1118T>A	p.Leu373Gln	missense_variant	9/9	1		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461638 Hom.: 0 Cov.: 61 AF XY: 0.00000138 AC XY: 1 AN XY: 727112

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2023

The c.1118T>A (p.L373Q) alteration is located in exon 8 (coding exon 8) of the CNPPD1 gene. This alteration results from a T to A substitution at nucleotide position 1118, causing the leucine (L) at amino acid position 373 to be replaced by a glutamine (Q). 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	Benign	0.074
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0035	T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.65	.;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.97	L;L
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.65	N;N
REVEL	Benign	0.061
Sift	Benign	0.14	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.0070	B;B
Vest4		0.21
MutPred		0.29		Gain of disorder (P = 0.0338);Gain of disorder (P = 0.0338);
MVP		0.26
MPC		0.24
ClinPred		0.11	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.085
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-220037423;