2-219172675-C-T

Variant names:

• chr2-219172675-C-T
• NM_015680.6:c.1144G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_015680.6(CNPPD1):​c.1144G>A​(p.Val382Met) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNPPD1 NM_015680.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.772

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061992317).
• BP6: Variant 2-219172675-C-T is Benign according to our data. Variant chr2-219172675-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3494531.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNPPD1	NM_015680.6	c.1144G>A	p.Val382Met	missense_variant	Exon 8 of 8	ENST00000360507.10	NP_056495.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNPPD1	ENST00000360507.10	c.1144G>A	p.Val382Met	missense_variant	Exon 8 of 8	1	NM_015680.6	ENSP00000353698.5
CNPPD1	ENST00000409789.5	c.1144G>A	p.Val382Met	missense_variant	Exon 9 of 9	1		ENSP00000386277.1
CNPPD1	ENST00000453038.5	c.*219G>A		downstream_gene_variant		2		ENSP00000410109.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 61

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 19, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.0
DANN	Benign	0.77
DEOGEN2	Benign	0.00093	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.65	.;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.062	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.26	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.020	N;N
REVEL	Benign	0.054
Sift	Benign	0.095	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.0	B;B
Vest4		0.067
MutPred		0.27		Gain of disorder (P = 0.069);Gain of disorder (P = 0.069);
MVP		0.25
MPC		0.23
ClinPred		0.079	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.024
gMVP		0.18

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: chr2-220037397;