11-67507596-A-T

Variant names:

• chr11-67507596-A-T
• rs1866560618
• NM_005851.5:c.176T>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005851.5(CDK2AP2):​c.176T>A​(p.Val59Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,238 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CDK2AP2 NM_005851.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.80

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK2AP2	NM_005851.5	c.176T>A	p.Val59Glu	missense_variant	Exon 2 of 4	ENST00000301488.8	NP_005842.1
CDK2AP2	NM_001271849.2	c.11T>A	p.Val4Glu	missense_variant	Exon 2 of 4		NP_001258778.1
CDK2AP2	NR_073484.2	n.567T>A		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK2AP2	ENST00000301488.8	c.176T>A	p.Val59Glu	missense_variant	Exon 2 of 4	1	NM_005851.5	ENSP00000301488.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461238 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726920

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 28, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.176T>A (p.V59E) alteration is located in exon 2 (coding exon 2) of the CDK2AP2 gene. This alteration results from a T to A substitution at nucleotide position 176, causing the valine (V) at amino acid position 59 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.085	T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.0073	T
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.0	L;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.72	N;N
REVEL	Benign	0.21
Sift	Uncertain	0.014	D;D
Sift4G	Benign	0.19	T;T
Polyphen		0.97	D;.
Vest4		0.74
MutPred		0.39		Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);
MVP		0.62
MPC		2.8
ClinPred		0.96	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.86

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: rs1866560618; hg19: chr11-67275067;