Variant 16-22347011-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001802.2(CDR2):c.1319T>C(p.Ile440Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

CDR2
NM_001802.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

Variant links:

Genes affected

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

CDR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.768

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDR2	NM_001802.2 link	c.1319T>C	p.Ile440Thr	missense_variant	5/5	ENST00000268383.7	NP_001793.1	Q01850
CDR2	XM_024450143.2 link	c.1094T>C	p.Ile365Thr	missense_variant	4/4		XP_024305911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDR2	ENST00000268383.7 link	c.1319T>C	p.Ile440Thr	missense_variant	5/5	1	NM_001802.2	ENSP00000268383.2		Q01850

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461726

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.1319T>C (p.I440T) alteration is located in exon 5 (coding exon 5) of the CDR2 gene. This alteration results from a T to C substitution at nucleotide position 1319, causing the isoleucine (I) at amino acid position 440 to be replaced by a threonine (T). 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.043

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.3

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.1

REVEL

Benign

0.14

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0060

Polyphen

0.99

Vest4

0.67

MutPred

0.20

Loss of stability (P = 0.0116);

MVP

0.84

MPC

0.98

ClinPred

0.91

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over