16-22347576-C-T

Variant names:

• chr16-22347576-C-T
• NM_001802.2:c.754G>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.754G>A​(p.Ala252Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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. A252P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CDR2 NM_001802.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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=0.1680716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDR2	NM_001802.2	c.754G>A	p.Ala252Thr	missense_variant	Exon 5 of 5	ENST00000268383.7	NP_001793.1
CDR2	XM_024450143.2	c.529G>A	p.Ala177Thr	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.754G>A	p.Ala252Thr	missense_variant	Exon 5 of 5	1	NM_001802.2	ENSP00000268383.2
CDR2	ENST00000564542.5	c.601G>A	p.Ala201Thr	missense_variant	Exon 7 of 7	5		ENSP00000457432.1
CDR2	ENST00000567406.5	c.*179G>A		downstream_gene_variant		4		ENSP00000457289.1
CDR2	ENST00000561630.1	n.*500G>A		downstream_gene_variant		5		ENSP00000455915.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461842 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.10
Sift	Benign	0.043	D;D
Sift4G	Benign	0.40	T;T
Polyphen		0.0030	B;.
Vest4		0.051
MutPred		0.19		Gain of catalytic residue at A252 (P = 0.1744);.;
MVP		0.82
MPC		0.74
ClinPred		0.81	D
GERP RS		4.6
Varity_R		0.11

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: chr16-22358897;