16-22347544-C-A

Variant names:

• chr16-22347544-C-A
• NM_001802.2:c.786G>T

Variant summary

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

The NM_001802.2(CDR2):​c.786G>T​(p.Gln262His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CDR2 NM_001802.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61

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=0.19036403).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDR2	NM_001802.2	c.786G>T	p.Gln262His	missense_variant	Exon 5 of 5	ENST00000268383.7	NP_001793.1
CDR2	XM_024450143.2	c.561G>T	p.Gln187His	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.786G>T	p.Gln262His	missense_variant	Exon 5 of 5	1	NM_001802.2	ENSP00000268383.2
CDR2	ENST00000564542.5	c.633G>T	p.Gln211His	missense_variant	Exon 7 of 7	5		ENSP00000457432.1
CDR2	ENST00000567406.5	c.*211G>T		downstream_gene_variant		4		ENSP00000457289.1
CDR2	ENST00000561630.1	n.*532G>T		downstream_gene_variant		5		ENSP00000455915.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461824 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727220

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.786G>T (p.Q262H) alteration is located in exon 5 (coding exon 5) of the CDR2 gene. This alteration results from a G to T substitution at nucleotide position 786, causing the glutamine (Q) at amino acid position 262 to be replaced by a histidine (H). 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	0.12
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.52	D;.
Eigen	Benign	-0.0053
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.033	D;D
Polyphen		0.93	P;.
Vest4		0.45
MutPred		0.28		Gain of catalytic residue at E264 (P = 0.1193);.;
MVP		0.81
MPC		0.26
ClinPred		0.86	D
GERP RS		3.8
Varity_R		0.16

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: chr16-22358865;