2-219171668-A-G

Variant names:

• chr2-219171668-A-G
• rs6436122
• NM_015680.6:c.*918T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015680.6(CNPPD1):​c.*918T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,208 control chromosomes in the GnomAD database, including 57,946 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.86 (57946 hom., cov: 32)
• Consequence: CNPPD1 NM_015680.6 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNPPD1	NM_015680.6	c.*918T>C		downstream_gene_variant		ENST00000360507.10	NP_056495.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNPPD1	ENST00000360507.10	c.*918T>C		downstream_gene_variant		1	NM_015680.6	ENSP00000353698.5

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131442 AN: 152090 Hom.: 57925 Cov.: 32

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.964

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.946

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.960

Gnomad OTH AF: 0.873

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.864 AC: 131515 AN: 152208 Hom.: 57946 Cov.: 32 AF XY: 0.859 AC XY: 63917 AN XY: 74418

African (AFR) AF: 0.745 AC: 30904 AN: 41506

American (AMR) AF: 0.810 AC: 12388 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.964 AC: 3347 AN: 3472

East Asian (EAS) AF: 0.482 AC: 2487 AN: 5164

South Asian (SAS) AF: 0.846 AC: 4080 AN: 4824

European-Finnish (FIN) AF: 0.946 AC: 10033 AN: 10610

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.960 AC: 65312 AN: 68026

Other (OTH) AF: 0.867 AC: 1830 AN: 2110

Alfa AF: 0.926 Hom.: 277427

Bravo AF: 0.845

Asia WGS AF: 0.647 AC: 2254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.017
DANN	Benign	0.34
PhyloP100		-2.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6436122; hg19: chr2-220036390;