12-55971915-C-T

Variant names:

• chr12-55971915-C-T
• rs2069414
• NM_001798.5:c.*290C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001798.5(CDK2):​c.*290C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000516 in 193,804 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000052 (0 hom.)
• Consequence: CDK2 NM_001798.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 11 publications found

Genes affected

CDK2 (HGNC:1771): (cyclin dependent kinase 2) This gene encodes a member of a family of serine/threonine protein kinases that participate in cell cycle regulation. The encoded protein is the catalytic subunit of the cyclin-dependent protein kinase complex, which regulates progression through the cell cycle. Activity of this protein is especially critical during the G1 to S phase transition. This protein associates with and regulated by other subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A), and p27Kip1 (CDKN1B). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

PMEL (HGNC:10880): (premelanosome protein) This gene encodes a melanocyte-specific type I transmembrane glycoprotein. The encoded protein is enriched in melanosomes, which are the melanin-producing organelles in melanocytes, and plays an essential role in the structural organization of premelanosomes. This protein is involved in generating internal matrix fibers that define the transition from Stage I to Stage II melanosomes. This protein undergoes a complex pattern of prosttranslational processing and modification that is essential to the proper functioning of the protein. A secreted form of this protein that is released by proteolytic ectodomain shedding may be used as a melanoma-specific serum marker. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001798.5. 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
	CDK2	NM_001798.5	MANE Select	c.*290C>T		3_prime_UTR	Exon 7 of 7	NP_001789.2
	CDK2	NM_052827.4		c.*290C>T		3_prime_UTR	Exon 6 of 6	NP_439892.2	P24941-2
	CDK2	NM_001290230.2		c.*290C>T		3_prime_UTR	Exon 5 of 5	NP_001277159.1	E7ESI2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK2	ENST00000266970.9	TSL:1 MANE Select	c.*290C>T		3_prime_UTR	Exon 7 of 7	ENSP00000266970.4	P24941-1
	CDK2	ENST00000553376.5	TSL:5	c.*290C>T		3_prime_UTR	Exon 8 of 8	ENSP00000452514.1	G3V5T9
	PMEL	ENST00000549233.2	TSL:5	c.-95-148G>A		intron	N/A	ENSP00000448871.1	F8VYZ1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000516 AC: 1 AN: 193804 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 99612

African (AFR) AF: 0.000186 AC: 1 AN: 5390

American (AMR) AF: 0.00 AC: 0 AN: 7422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6892

East Asian (EAS) AF: 0.00 AC: 0 AN: 14010

South Asian (SAS) AF: 0.00 AC: 0 AN: 11638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 982

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 122228

Other (OTH) AF: 0.00 AC: 0 AN: 12556

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 512

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.25
DANN	Benign	0.67
PhyloP100		-1.8

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: rs2069414; hg19: chr12-56365699;