16-22347246-C-T

Variant names:

• chr16-22347246-C-T
• NM_001802.2:c.1084G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001802.2(CDR2):​c.1084G>A​(p.Glu362Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDR2 NM_001802.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.63

Genes affected

CDR2 (HGNC:1799): (cerebellar degeneration related protein 2) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41679353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDR2	NM_001802.2	c.1084G>A	p.Glu362Lys	missense_variant	Exon 5 of 5	ENST00000268383.7	NP_001793.1
CDR2	XM_024450143.2	c.859G>A	p.Glu287Lys	missense_variant	Exon 4 of 4		XP_024305911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDR2	ENST00000268383.7	c.1084G>A	p.Glu362Lys	missense_variant	Exon 5 of 5	1	NM_001802.2	ENSP00000268383.2
CDR2	ENST00000564542.5	c.*229G>A		downstream_gene_variant		5		ENSP00000457432.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1084G>A (p.E362K) alteration is located in exon 5 (coding exon 5) of the CDR2 gene. This alteration results from a G to A substitution at nucleotide position 1084, causing the glutamic acid (E) at amino acid position 362 to be replaced by a lysine (K). 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	Benign	0.20
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.86	D
Eigen	Benign	0.10
Eigen_PC	Benign	0.097
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.27
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.017	D
Polyphen		0.68	P
Vest4		0.51
MutPred		0.30		Loss of ubiquitination at K365 (P = 0.0234);
MVP		0.54
MPC		0.82
ClinPred		0.94	D
GERP RS		4.8
Varity_R		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-22358567;