Variant 2-159798186-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014880.5(CD302):c.13G>A(p.Ala5Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000259 in 1,468,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

CD302
NM_014880.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.787

Variant links:

Genes affected

CD302 (HGNC:30843): (CD302 molecule) CD302 is a C-type lectin receptor involved in cell adhesion and migration, as well as endocytosis and phagocytosis (Kato et al., 2007 [PubMed 17947679]).[supplied by OMIM, Aug 2008]

CD302 links:

LY75-CD302 (HGNC:38828): (LY75-CD302 readthrough) This locus represents naturally occurring read-through transcription between the neighboring lymphocyte antigen 75 (LY75) and CD302 molecule (CD302) genes. Alternative splicing results in multiple transcript variants encoding fusion products that share sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

LY75-CD302 links:

CD302 (HGNC:):

CD302 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0042333603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD302	NM_014880.5 linkuse as main transcript	c.13G>A	p.Ala5Thr	missense_variant	1/6	ENST00000259053.6	NP_055695.2	Q8IX05-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD302	ENST00000259053.6 linkuse as main transcript	c.13G>A	p.Ala5Thr	missense_variant	1/6	1	NM_014880.5	ENSP00000259053.4		Q8IX05-1
LY75-CD302	ENST00000504764.5 linkuse as main transcript	c.4990+8787G>A		intron_variant		2		ENSP00000423463.1

Frequencies

GnomAD3 genomes

AF:

0.0000735

AC:

AN:

149750

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000486

GnomAD3 exomes

AF:

0.000176

AC:

AN:

79732

Hom.:

AF XY:

0.000219

AC XY:

AN XY:

45706

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00325

Gnomad SAS exome

AF:

0.000179

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000434

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1318280

Hom.:

Cov.:

AF XY:

0.0000185

AC XY:

AN XY:

650222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000566

Gnomad4 SAS exome

AF:

0.0000687

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.54e-7

Gnomad4 OTH exome

AF:

0.0000917

GnomAD4 genome

AF:

0.0000734

AC:

AN:

149842

Hom.:

Cov.:

AF XY:

0.0000682

AC XY:

AN XY:

73284

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000481

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.000206

AC:

Asia WGS

AF:

0.00289

AC:

AN:

3470

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 28, 2023

The c.13G>A (p.A5T) alteration is located in exon 1 (coding exon 1) of the CD302 gene. This alteration results from a G to A substitution at nucleotide position 13, causing the alanine (A) at amino acid position 5 to be replaced by a threonine (T). 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

0.30

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.5

DANN

Benign

0.87

DEOGEN2

Benign

0.098

.;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.35

T;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.0042

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.;N

PROVEAN

Benign

0.22

N;.;N

REVEL

Benign

0.012

Sift

Benign

0.17

T;.;T

Sift4G

Benign

0.23

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.19

MutPred

0.33

Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);

MVP

0.14

MPC

0.047

ClinPred

0.012

GERP RS

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.039

gMVP

0.31

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