16-30353677-G-A

Variant names:

• chr16-30353677-G-A
• rs2049505547
• NM_006110.3:c.499C>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3 BS2

The NM_006110.3(CD2BP2):​c.499C>T​(p.Pro167Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CD2BP2 NM_006110.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.15

Genes affected

CD2BP2 (HGNC:1656): (CD2 cytoplasmic tail binding protein 2) This gene encodes a bi-functional protein. In the cytoplasm, the encoded protein binds the cytoplasmic tail of human surface antigen CD2 via its C-terminal GYF domain, and regulate CD2-triggered T lymphocyte activation. In the nucleus, this protein is a component of the U5 small nuclear ribonucleoprotein complex and is involved in RNA splicing. A pseudogene has been identified on chromosome 7. Alternative splicing results in multiple transcript variants but their biological validity has not been determined. [provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.771
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD2BP2	NM_006110.3	c.499C>T	p.Pro167Ser	missense_variant	Exon 5 of 7	ENST00000305596.8	NP_006101.1
CD2BP2	NM_001243646.2	c.499C>T	p.Pro167Ser	missense_variant	Exon 4 of 6		NP_001230575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD2BP2	ENST00000305596.8	c.499C>T	p.Pro167Ser	missense_variant	Exon 5 of 7	1	NM_006110.3	ENSP00000304903.3
CD2BP2	ENST00000569466.1	c.499C>T	p.Pro167Ser	missense_variant	Exon 4 of 6	1		ENSP00000456935.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461542 Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5 AN XY: 727082

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: 0.00000630

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.499C>T (p.P167S) alteration is located in exon 5 (coding exon 4) of the CD2BP2 gene. This alteration results from a C to T substitution at nucleotide position 499, causing the proline (P) at amino acid position 167 to be replaced by a serine (S). 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	Uncertain	0.50
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.71	.;T
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-6.8	D;D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		1.0	D;D
Vest4		0.69
MutPred		0.29		Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);
MVP		0.70
MPC		0.38
ClinPred		1.0	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.83
gMVP		0.72

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

LitVar

Other links and lift over

dbSNP: rs2049505547; hg19: chr16-30364998;