Variant chr2-159875493-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002349.4(LY75):c.1925C>T(p.Pro642Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LY75
NM_002349.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.35

Variant links:

Genes affected

LY75 (HGNC:6729): (lymphocyte antigen 75) Predicted to enable signaling receptor activity. Predicted to be involved in immune response and inflammatory response. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

LY75 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:

LY75 (HGNC:):

LY75 links:

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ACMG classification

Classification made for transcript

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=0.26108307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY75	NM_002349.4 linkuse as main transcript	c.1925C>T	p.Pro642Leu	missense_variant	12/35	ENST00000263636.5	NP_002340.2	O60449-1Q59H44
LY75-CD302	NM_001198759.1 linkuse as main transcript	c.1925C>T	p.Pro642Leu	missense_variant	12/39		NP_001185688.1	O60449-2
LY75-CD302	NM_001198760.1 linkuse as main transcript	c.1925C>T	p.Pro642Leu	missense_variant	12/38		NP_001185689.1	O60449-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LY75	ENST00000263636.5 linkuse as main transcript	c.1925C>T	p.Pro642Leu	missense_variant	12/35	1	NM_002349.4	ENSP00000263636.4	O60449-1
LY75-CD302	ENST00000504764.5 linkuse as main transcript	c.1925C>T	p.Pro642Leu	missense_variant	12/39	2		ENSP00000423463.1
LY75	ENST00000484559.1 linkuse as main transcript	n.1985C>T		non_coding_transcript_exon_variant	12/13	1
LY75-CD302	ENST00000505052.1 linkuse as main transcript	c.1925C>T	p.Pro642Leu	missense_variant	12/38	2		ENSP00000421035.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461818

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727204

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 01, 2024

The c.1925C>T (p.P642L) alteration is located in exon 12 (coding exon 12) of the LY75-CD302 gene. This alteration results from a C to T substitution at nucleotide position 1925, causing the proline (P) at amino acid position 642 to be replaced by a leucine (L). 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

0.072

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

.;.;D

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.4

.;.;M

PROVEAN

Pathogenic

-5.0

D;D;D

REVEL

Benign

0.098

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.97

.;.;D

Vest4

0.18

MutPred

0.32

Loss of disorder (P = 0.0402);Loss of disorder (P = 0.0402);Loss of disorder (P = 0.0402);

MVP

0.30

MPC

0.33

ClinPred

0.97

GERP RS

3.9

Varity_R

0.17

gMVP

0.47

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over