NM_006110.3:c.895T>G

Variant names:

• chr16-30353201-A-C
• rs2049498212
• NM_006110.3:c.895T>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_006110.3(CD2BP2):​c.895T>G​(p.Phe299Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 0.00020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD2BP2 NM_006110.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.958

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006110.3. 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
	CD2BP2	NM_006110.3	MANE Select	c.895T>G	p.Phe299Val	missense	Exon 6 of 7	NP_006101.1	O95400
	CD2BP2	NM_001243646.2		c.895T>G	p.Phe299Val	missense	Exon 5 of 6	NP_001230575.1	A0A024QZC1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2BP2	ENST00000305596.8	TSL:1 MANE Select	c.895T>G	p.Phe299Val	missense	Exon 6 of 7	ENSP00000304903.3	O95400
	CD2BP2	ENST00000569466.1	TSL:1	c.895T>G	p.Phe299Val	missense	Exon 5 of 6	ENSP00000456935.1	O95400
	CD2BP2	ENST00000921036.1		c.895T>G	p.Phe299Val	missense	Exon 6 of 7	ENSP00000591095.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000204 AC: 286 AN: 1400612 Hom.: 0 Cov.: 32 AF XY: 0.000166 AC XY: 116 AN XY: 699312

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000186 AC: 6 AN: 32220

American (AMR) AF: 0.00 AC: 0 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25756

East Asian (EAS) AF: 0.0000761 AC: 3 AN: 39404

South Asian (SAS) AF: 0.0000353 AC: 3 AN: 85012

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 0.000249 AC: 263 AN: 1056370

Other (OTH) AF: 0.000171 AC: 10 AN: 58312

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		5.8
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.042	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.86		Gain of phosphorylation at Y296 (P = 0.0956)
MVP		0.71
MPC		0.49
ClinPred		1.0	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.86
gMVP		0.88

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: rs2049498212; hg19: chr16-30364522;