16-22347086-G-A

Position:

• chr16-22347086-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001802.2(CDR2):​c.1244C>T​(p.Ser415Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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: 1.17

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16962105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDR2	NM_001802.2	c.1244C>T	p.Ser415Phe	missense_variant	5/5	ENST00000268383.7	NP_001793.1
CDR2	XM_024450143.2	c.1019C>T	p.Ser340Phe	missense_variant	4/4		XP_024305911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDR2	ENST00000268383.7	c.1244C>T	p.Ser415Phe	missense_variant	5/5	1	NM_001802.2	ENSP00000268383	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 05, 2022

The c.1244C>T (p.S415F) alteration is located in exon 5 (coding exon 5) of the CDR2 gene. This alteration results from a C to T substitution at nucleotide position 1244, causing the serine (S) at amino acid position 415 to be replaced by a phenylalanine (F). 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	0.084
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.044
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.018	D
Polyphen		0.63	P
Vest4		0.13
MutPred		0.19		Loss of glycosylation at S415 (P = 0.0078);
MVP		0.62
MPC		0.46
ClinPred		0.29	T
GERP RS		3.6
Varity_R		0.047

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: chr16-22358407;