Variant chr2-203706740-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006139.4(CD28):c.44A>G(p.Gln15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000892 in 1,457,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

CD28
NM_006139.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.67

Variant links:

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]

CD28 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35332346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CD28	NM_006139.4 linkuse as main transcript	c.44A>G	p.Gln15Arg	missense_variant	1/4	ENST00000324106.9
CD28	NM_001243077.2 linkuse as main transcript	c.44A>G	p.Gln15Arg	missense_variant	1/4
CD28	NM_001243078.2 linkuse as main transcript	c.44A>G	p.Gln15Arg	missense_variant	1/3
CD28	NM_001410981.1 linkuse as main transcript	c.94+123A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD28	ENST00000324106.9 linkuse as main transcript	c.44A>G	p.Gln15Arg	missense_variant	1/4	1	NM_006139.4	P1	P10747-1
CD28	ENST00000374481.7 linkuse as main transcript	c.44A>G	p.Gln15Arg	missense_variant	1/3	1			P10747-2
CD28	ENST00000458610.6 linkuse as main transcript	c.94+123A>G		intron_variant		1			P10747-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000892

AC:

AN:

1457590

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

725402

show subpopulations

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:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 21, 2024

The c.44A>G (p.Q15R) alteration is located in exon 1 (coding exon 1) of the CD28 gene. This alteration results from a A to G substitution at nucleotide position 44, causing the glutamine (Q) at amino acid position 15 to be replaced by an arginine (R). 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

0.11

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Uncertain

0.58

.;D

Eigen

Benign

-0.056

Eigen_PC

Benign

0.037

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.35

T;T

M_CAP

Benign

0.075

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.6

N;N

REVEL

Uncertain

0.38

Sift

Benign

0.053

T;D

Sift4G

Benign

0.071

T;T

Polyphen

0.095

B;P

Vest4

0.42

MutPred

0.41

Loss of sheet (P = 0.0084);Loss of sheet (P = 0.0084);

MVP

0.88

MPC

0.21

ClinPred

0.84

GERP RS

5.7

Varity_R

0.23

gMVP

0.64

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over