11-67507596-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005851.5(CDK2AP2):​c.176T>G​(p.Val59Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V59E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CDK2AP2 NM_005851.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.80
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32188314).

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.176T>G	p.Val59Gly	missense	Exon 2 of 4	NP_005842.1	O75956
	CDK2AP2	NM_001271849.2		c.11T>G	p.Val4Gly	missense	Exon 2 of 4	NP_001258778.1
	CDK2AP2	NR_073484.2		n.567T>G		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK2AP2	ENST00000301488.8	TSL:1 MANE Select	c.176T>G	p.Val59Gly	missense	Exon 2 of 4	ENSP00000301488.4	O75956
	CDK2AP2	ENST00000531178.1	TSL:1	n.*131T>G		non_coding_transcript_exon	Exon 2 of 4	ENSP00000436213.1	E9PQJ3
	CDK2AP2	ENST00000531178.1	TSL:1	n.*131T>G		3_prime_UTR	Exon 2 of 4	ENSP00000436213.1	E9PQJ3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461238 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726920

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111976

Other (OTH) AF: 0.0000331 AC: 2 AN: 60384

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.8
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.91	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.010	D
Sift4G	Benign	0.19	T
Polyphen		0.95	P
Vest4		0.49
MutPred		0.35		Loss of sheet (P = 0.0181)
MVP		0.57
MPC		2.5
ClinPred		0.90	D
GERP RS		5.3
PromoterAI		-0.0032	Neutral
Varity_R		0.30
gMVP		0.84
Mutation Taster		=78/22	polymorphism

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: rs1866560618; hg19: chr11-67275067;