chr2-203706748-G-A

Position:

• chr2-203706748-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_006139.4(CD28):​c.52G>A​(p.Gly18Arg) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CD28 NM_006139.4 missense, splice_region
• Scores: Splicing: ADA: 0.9999
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.47

Genes affected

CD28 (HGNC:1653): (CD28 molecule) The protein encoded by this gene is essential for T-cell proliferation and survival, cytokine production, and T-helper type-2 development. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-203706748-G-A is Pathogenic according to our data. Variant chr2-203706748-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 3256912.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD28	NM_006139.4	c.52G>A	p.Gly18Arg	missense_variant, splice_region_variant	1/4	ENST00000324106.9	NP_006130.1
CD28	NM_001243077.2	c.52G>A	p.Gly18Arg	missense_variant, splice_region_variant	1/4		NP_001230006.1
CD28	NM_001243078.2	c.52G>A	p.Gly18Arg	missense_variant, splice_region_variant	1/3		NP_001230007.1
CD28	NM_001410981.1	c.94+131G>A		intron_variant			NP_001397910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD28	ENST00000324106.9	c.52G>A	p.Gly18Arg	missense_variant, splice_region_variant	1/4	1	NM_006139.4	ENSP00000324890.7
CD28	ENST00000374481.7	c.52G>A	p.Gly18Arg	missense_variant, splice_region_variant	1/3	1		ENSP00000363605.4
CD28	ENST00000458610.6	c.94+131G>A		intron_variant		1		ENSP00000393648.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Immunodeficiency 123 with HPV-related verrucosis Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	30
DANN	Benign	0.97
DEOGEN2	Benign	0.40	.;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.47	T;T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Uncertain	0.0095	D
MutationAssessor	Benign	1.2	L;L
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.4	N;N
REVEL	Uncertain	0.43
Sift	Benign	0.10	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.92	P;B
Vest4		0.36
MutPred		0.37		Gain of sheet (P = 0.0043);Gain of sheet (P = 0.0043);
MVP		0.82
MPC		0.24
ClinPred		0.68	D
GERP RS		5.5
Varity_R		0.16
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.99
SpliceAI score (max)		0.77		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.77		Position offset: 0

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: chr2-204571471;