16-22347038-C-T

Variant names:

• chr16-22347038-C-T
• rs1250563028
• NM_001802.2:c.1292G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001802.2(CDR2):​c.1292G>A​(p.Ser431Asn) 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. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S431T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDR2 NM_001802.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2737674).

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.1292G>A	p.Ser431Asn	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.1292G>A	p.Ser431Asn	missense	Exon 5 of 5	ENSP00000268383.2	Q01850
	CDR2	ENST00000961655.1		c.1277G>A	p.Ser426Asn	missense	Exon 5 of 5	ENSP00000631714.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.047
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.1
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.095
Sift	Benign	0.039	D
Sift4G	Benign	0.062	T
Polyphen		0.015	B
Vest4		0.24
MutPred		0.22		Loss of disorder (P = 0.0676)
MVP		0.79
MPC		0.23
ClinPred		0.72	D
GERP RS		4.7
Varity_R		0.21

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: rs1250563028; hg19: chr16-22358359;