chr12-55972195-G-A

Variant names:

• chr12-55972195-G-A
• rs2069415
• NM_001798.5:c.*570G>A

Variant summary

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

The NM_001798.5(CDK2):​c.*570G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 152,262 control chromosomes in the GnomAD database, including 55 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 0.014 (55 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDK2 NM_001798.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

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.*570G>A		3_prime_UTR	Exon 7 of 7	NP_001789.2
	CDK2	NM_052827.4		c.*570G>A		3_prime_UTR	Exon 6 of 6	NP_439892.2	P24941-2
	CDK2	NM_001290230.2		c.*570G>A		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.*570G>A		3_prime_UTR	Exon 7 of 7	ENSP00000266970.4	P24941-1
	PMEL	ENST00000549233.2	TSL:5	c.-95-428C>T		intron	N/A	ENSP00000448871.1	F8VYZ1
	CDK2	ENST00000555408.5	TSL:3	n.*2079G>A		non_coding_transcript_exon	Exon 6 of 6	ENSP00000450983.1	G3V317

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2104 AN: 152144 Hom.: 54 Cov.: 31

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0365

Gnomad FIN AF: 0.00424

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.00573

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 226 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 126

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 8

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 196

Other (OTH) AF: 0.00 AC: 0 AN: 10

GnomAD4 genome AF: 0.0138 AC: 2103 AN: 152262 Hom.: 55 Cov.: 31 AF XY: 0.0148 AC XY: 1103 AN XY: 74450

African (AFR) AF: 0.0266 AC: 1106 AN: 41534

American (AMR) AF: 0.00399 AC: 61 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.124 AC: 645 AN: 5182

South Asian (SAS) AF: 0.0364 AC: 175 AN: 4812

European-Finnish (FIN) AF: 0.00424 AC: 45 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 68026

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.00335 Hom.: 17

Bravo AF: 0.0152

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.64
DANN	Benign	0.50
PhyloP100		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2069415; hg19: chr12-56365979;