Variant chr2-159805093-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.5120C>T(p.Ala1707Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

LY75
NM_002349.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

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:

Genome browser will be placed here

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=0.13727933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY75	NM_002349.4 linkuse as main transcript	c.5120C>T	p.Ala1707Val	missense_variant	35/35	ENST00000263636.5	NP_002340.2	O60449-1Q59H44
LY75-CD302	NM_001198759.1 linkuse as main transcript	c.4990+1880C>T		intron_variant			NP_001185688.1	O60449-2
LY75-CD302	NM_001198760.1 linkuse as main transcript	c.4822+3356C>T		intron_variant			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.5120C>T	p.Ala1707Val	missense_variant	35/35	1	NM_002349.4	ENSP00000263636.4	O60449-1
LY75-CD302	ENST00000504764.5 linkuse as main transcript	c.4990+1880C>T		intron_variant		2		ENSP00000423463.1
LY75-CD302	ENST00000505052.1 linkuse as main transcript	c.4822+3356C>T		intron_variant		2		ENSP00000421035.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251254

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461782

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727202

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000223

Hom.:

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 06, 2024

The c.5120C>T (p.A1707V) alteration is located in exon 35 (coding exon 35) of the LY75 gene. This alteration results from a C to T substitution at nucleotide position 5120, causing the alanine (A) at amino acid position 1707 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.088

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.77

M_CAP

Benign

0.011

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PROVEAN

Benign

-0.21

REVEL

Benign

0.081

Sift

Benign

0.045

Sift4G

Uncertain

0.034

Polyphen

0.16

Vest4

0.063

MutPred

0.69

Loss of loop (P = 0.0986);

MVP

0.13

ClinPred

0.061

GERP RS

3.3

Varity_R

0.035

gMVP

0.48

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