12-123261262-G-T

Variant names:

• chr12-123261262-G-T
• rs6633
• NM_004642.4:c.*474C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004642.4. 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
	CDK2AP1	NM_004642.4	MANE Select	c.*474C>A		3_prime_UTR	Exon 4 of 4	NP_004633.1	O14519-1
	CDK2AP1	NM_001270433.2		c.*474C>A		3_prime_UTR	Exon 4 of 4	NP_001257362.1	O14519-2
	CDK2AP1	NM_001270434.2		c.*474C>A		3_prime_UTR	Exon 4 of 4	NP_001257363.1	O14519-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK2AP1	ENST00000261692.7	TSL:1 MANE Select	c.*474C>A		3_prime_UTR	Exon 4 of 4	ENSP00000261692.2	O14519-1
	CDK2AP1	ENST00000535979.5	TSL:3	c.*474C>A		3_prime_UTR	Exon 4 of 4	ENSP00000442565.1	O14519-2
	CDK2AP1	ENST00000538446.5	TSL:5	c.*474C>A		3_prime_UTR	Exon 4 of 4	ENSP00000442502.1	O14519-2

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

African (AFR) AF: 0.125 AC: 1 AN: 8

American (AMR) AF: 0.151 AC: 23 AN: 152

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 2 AN: 10

East Asian (EAS) AF: 0.00 AC: 0 AN: 14

South Asian (SAS) AF: 0.250 AC: 24 AN: 96

European-Finnish (FIN) AF: 0.100 AC: 2 AN: 20

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.157 AC: 122 AN: 776

Other (OTH) AF: 0.167 AC: 6 AN: 36

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

African (AFR) AF: 0.0823 AC: 3416 AN: 41522

American (AMR) AF: 0.183 AC: 2785 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 864 AN: 3468

East Asian (EAS) AF: 0.00424 AC: 22 AN: 5186

South Asian (SAS) AF: 0.217 AC: 1047 AN: 4824

European-Finnish (FIN) AF: 0.224 AC: 2370 AN: 10580

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13612 AN: 67994

Other (OTH) AF: 0.170 AC: 358 AN: 2112

Alfa AF: 0.132 Hom.: 347

Bravo AF: 0.155

Asia WGS AF: 0.101 AC: 352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
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: rs6633; hg19: chr12-123745809;