chr2-159771955-A-G

Position:

• chr2-159771955-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014880.5(CD302):​c.595T>C​(p.Ser199Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD302 NM_014880.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75

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]

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]

CD302 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13934654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD302	NM_014880.5	c.595T>C	p.Ser199Pro	missense_variant	6/6	ENST00000259053.6	NP_055695.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD302	ENST00000259053.6	c.595T>C	p.Ser199Pro	missense_variant	6/6	1	NM_014880.5	ENSP00000259053.4
LY75-CD302	ENST00000504764.5	c.5518T>C	p.Ser1840Pro	missense_variant	39/39	2		ENSP00000423463.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.5518T>C (p.S1840P) alteration is located in exon 39 (coding exon 39) of the LY75-CD302 gene. This alteration results from a T to C substitution at nucleotide position 5518, causing the serine (S) at amino acid position 1840 to be replaced by a proline (P). 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	0.087
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	.;.;T;.;.
Eigen	Benign	-0.086
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.73	T;T;T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	.;.;M;.;.
PROVEAN	Uncertain	-2.7	D;.;D;N;N
REVEL	Benign	0.094
Sift	Uncertain	0.020	D;.;D;D;D
Sift4G	Uncertain	0.053	T;T;T;T;T
Polyphen		0.95	.;.;P;.;.
Vest4		0.31
MutPred		0.29		.;.;Loss of glycosylation at S199 (P = 0.0644);.;.;
MVP		0.55
MPC		0.25, 0.36
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.41
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-160628466;