16-22347654-C-A

Variant names:

• chr16-22347654-C-A
• rs769723609
• NM_001802.2:c.676G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001802.2(CDR2):​c.676G>T​(p.Val226Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CDR2 NM_001802.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07363632).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001802.2. 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
	CDR2	NM_001802.2	MANE Select	c.676G>T	p.Val226Leu	missense	Exon 5 of 5	NP_001793.1	Q01850

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDR2	ENST00000268383.7	TSL:1 MANE Select	c.676G>T	p.Val226Leu	missense	Exon 5 of 5	ENSP00000268383.2	Q01850
	CDR2	ENST00000961655.1		c.661G>T	p.Val221Leu	missense	Exon 5 of 5	ENSP00000631714.1
	CDR2	ENST00000564542.5	TSL:5	c.523G>T	p.Val175Leu	missense	Exon 7 of 7	ENSP00000457432.1	H3BU23

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.0
DANN	Benign	0.97
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.070
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.070
Sift	Benign	0.30	T
Sift4G	Benign	0.54	T
Polyphen		0.024	B
Vest4		0.13
MutPred		0.16		Gain of loop (P = 0.1081)
MVP		0.39
MPC		0.24
ClinPred		0.14	T
GERP RS		4.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.024

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: rs769723609; hg19: chr16-22358975;