2-159882292-G-A

Position:

chr2-159882292-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002349.4(LY75):c.1078C>T(p.Arg360Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,613,804 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 5 hom. )

Consequence

LY75
NM_002349.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.62

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013620734).

BP6

Variant 2-159882292-G-A is Benign according to our data. Variant chr2-159882292-G-A is described in ClinVar as [Benign]. Clinvar id is 730667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY75	NM_002349.4 linkuse as main transcript	c.1078C>T	p.Arg360Cys	missense_variant	7/35	ENST00000263636.5	NP_002340.2	O60449-1Q59H44
LY75-CD302	NM_001198759.1 linkuse as main transcript	c.1078C>T	p.Arg360Cys	missense_variant	7/39		NP_001185688.1	O60449-2
LY75-CD302	NM_001198760.1 linkuse as main transcript	c.1078C>T	p.Arg360Cys	missense_variant	7/38		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.1078C>T	p.Arg360Cys	missense_variant	7/35	1	NM_002349.4	ENSP00000263636.4	O60449-1
LY75-CD302	ENST00000504764.5 linkuse as main transcript	c.1078C>T	p.Arg360Cys	missense_variant	7/39	2		ENSP00000423463.1
LY75	ENST00000484559.1 linkuse as main transcript	n.1138C>T		non_coding_transcript_exon_variant	7/13	1
LY75-CD302	ENST00000505052.1 linkuse as main transcript	c.1078C>T	p.Arg360Cys	missense_variant	7/38	2		ENSP00000421035.1

Frequencies

GnomAD3 genomes

AF:

0.00385

AC:

586

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00135

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00161

AC:

404

AN:

250666

Hom.:

AF XY:

0.00147

AC XY:

199

AN XY:

135464

show subpopulations

Gnomad AFR exome

AF:

0.0111

Gnomad AMR exome

AF:

0.000724

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.00107

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.000655

GnomAD4 exome

AF:

0.00146

AC:

2130

AN:

1461502

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

1006

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.0112

Gnomad4 AMR exome

AF:

0.000761

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00166

Gnomad4 FIN exome

AF:

0.000937

Gnomad4 NFE exome

AF:

0.00128

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00385

AC:

586

AN:

152302

Hom.:

Cov.:

AF XY:

0.00357

AC XY:

266

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0113

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00135

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00170

Hom.:

Bravo

AF:

0.00400

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00999

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00196

AC:

238

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.000949

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

.;.;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.61

LIST_S2

Uncertain

0.91

D;D;D

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

.;.;M

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Benign

0.15

Sift

Benign

0.043

D;D;D

Sift4G

Uncertain

0.022

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.35

MVP

0.26

MPC

0.24

ClinPred

0.038

GERP RS

5.6

Varity_R

0.11

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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