12-123261262-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004642.4(CDK2AP1):c.*474C>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 0.162 in 153,260 control chromosomes in the GnomAD database, including 2,365 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 0.16 (2347 hom., cov: 32)
  • Exomes 𝑓: 0.16 (18 hom.)
• Consequence: CDK2AP1 NM_004642.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

Genes affected

CDK2AP1 (HGNC:14002): (cyclin dependent kinase 2 associated protein 1) The protein encoded by this gene is a cyclin-dependent kinase 2 (CDK2) -associated protein which is thought to negatively regulate CDK2 activity by sequestering monomeric CDK2, and targeting CDK2 for proteolysis. This protein was found to also interact with DNA polymerase alpha/primase and mediate the phosphorylation of the large p180 subunit, which suggests a regulatory role in DNA replication during the S-phase of the cell cycle. This protein also forms a core subunit of the nucleosome remodeling and histone deacetylation (NURD) complex that epigenetically regulates embryonic stem cell differentiation. This gene thus plays a role in both cell-cycle and epigenetic regulation. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK2AP1	NM_004642.4	c.*474C>A		3_prime_UTR_variant	4/4	ENST00000261692.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK2AP1	ENST00000261692.7	c.*474C>A		3_prime_UTR_variant	4/4	1	NM_004642.4

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24701 AN: 152030 Hom.: 2339 Cov.: 32

Gnomad AFR AF: 0.0826

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.172

GnomAD4 exome AF: 0.162 AC: 180 AN: 1112 Hom.: 18 Cov.: 0 AF XY: 0.177 AC XY: 98 AN XY: 554

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.151

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.162 AC: 24708 AN: 152148 Hom.: 2347 Cov.: 32 AF XY: 0.164 AC XY: 12232 AN XY: 74392

Gnomad4 AFR AF: 0.0823

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.00424

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.170

Alfa AF: 0.132 Hom.: 316

Bravo AF: 0.155

Asia WGS AF: 0.101 AC: 352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	13
Dann	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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

LitVar

Other links and lift over

dbSNP: rs6633; hg19: chr12-123745809;