11-67507387-G-T

Variant names:

• chr11-67507387-G-T
• NM_005851.5:c.291C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005851.5(CDK2AP2):​c.291C>A​(p.Ser97Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDK2AP2 NM_005851.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0620
• Publications: 0 publications found

Genes affected

CDK2AP2 (HGNC:30833): (cyclin dependent kinase 2 associated protein 2) This gene encodes a protein that interacts with cyclin-dependent kinase 2 associated protein 1. Pseudogenes associated with this gene are located on chromosomes 7 and 9. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005851.5. 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
	CDK2AP2	NM_005851.5	MANE Select	c.291C>A	p.Ser97Arg	missense	Exon 3 of 4	NP_005842.1	O75956
	CDK2AP2	NM_001271849.2		c.126C>A	p.Ser42Arg	missense	Exon 3 of 4	NP_001258778.1
	CDK2AP2	NR_073484.2		n.682C>A		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK2AP2	ENST00000301488.8	TSL:1 MANE Select	c.291C>A	p.Ser97Arg	missense	Exon 3 of 4	ENSP00000301488.4	O75956
	CDK2AP2	ENST00000531178.1	TSL:1	n.*246C>A		non_coding_transcript_exon	Exon 3 of 4	ENSP00000436213.1	E9PQJ3
	CDK2AP2	ENST00000531178.1	TSL:1	n.*246C>A		3_prime_UTR	Exon 3 of 4	ENSP00000436213.1	E9PQJ3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.062
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.59
Sift	Benign	0.088	T
Sift4G	Benign	0.088	T
Polyphen		1.0	D
Vest4		0.89
MutPred		0.64		Gain of methylation at S97 (P = 0.0401)
MVP		0.26
MPC		2.4
ClinPred		0.99	D
GERP RS		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.76
gMVP		0.97
Mutation Taster		=18/82	disease causing

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

hg19: chr11-67274858;